A subclass of muscarinic receptor that mediates cholinergic-induced contraction in a variety of SMOOTH MUSCLES.
A specific subtype of muscarinic receptor that has a high affinity for the drug PIRENZEPINE. It is found in the peripheral GANGLIA where it signals a variety of physiological functions such as GASTRIC ACID secretion and BRONCHOCONSTRICTION. This subtype of muscarinic receptor is also found in neuronal tissues including the CEREBRAL CORTEX and HIPPOCAMPUS where it mediates the process of MEMORY and LEARNING.
One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for MUSCARINE over NICOTINE. There are several subtypes (usually M1, M2, M3....) that are characterized by their cellular actions, pharmacology, and molecular biology.
A specific subtype of muscarinic receptor found in the lower BRAIN, the HEART and in SMOOTH MUSCLE-containing organs. Although present in smooth muscle the M2 muscarinic receptor appears not to be involved in contractile responses.
Drugs that bind to but do not activate MUSCARINIC RECEPTORS, thereby blocking the actions of endogenous ACETYLCHOLINE or exogenous agonists. Muscarinic antagonists have widespread effects including actions on the iris and ciliary muscle of the eye, the heart and blood vessels, secretions of the respiratory tract, GI system, and salivary glands, GI motility, urinary bladder tone, and the central nervous system.
Drugs that bind to and activate muscarinic cholinergic receptors (RECEPTORS, MUSCARINIC). Muscarinic agonists are most commonly used when it is desirable to increase smooth muscle tone, especially in the GI tract, urinary bladder and the eye. They may also be used to reduce heart rate.
A specific subtype of muscarinic receptor found in the CORPUS STRIATUM and the LUNG. It has similar receptor binding specificities to MUSCARINIC RECEPTOR M1 and MUSCARINIC RECEPTOR M2.
A muscarinic antagonist used to study binding characteristics of muscarinic cholinergic receptors.
A specific subtype of muscarinic receptor found in a variety of locations including the SALIVARY GLANDS and the SUBSTANTIA NIGRA and VENTRAL TEGMENTAL AREA of the BRAIN.
Organic chemicals which have two amino groups in an aliphatic chain.
A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS.
Agents that inhibit the actions of the parasympathetic nervous system. The major group of drugs used therapeutically for this purpose is the MUSCARINIC ANTAGONISTS.
A synthetic nondepolarizing blocking drug. The actions of gallamine triethiodide are similar to those of TUBOCURARINE, but this agent blocks the cardiac vagus and may cause sinus tachycardia and, occasionally, hypertension and increased cardiac output. It should be used cautiously in patients at risk from increased heart rate but may be preferred for patients with bradycardia. (From AMA Drug Evaluations Annual, 1992, p198)
An antimuscarinic agent that inhibits gastric secretion at lower doses than are required to affect gastrointestinal motility, salivary, central nervous system, cardiovascular, ocular, and urinary function. It promotes the healing of duodenal ulcers and due to its cytoprotective action is beneficial in the prevention of duodenal ulcer recurrence. It also potentiates the effect of other antiulcer agents such as CIMETIDINE and RANITIDINE. It is generally well tolerated by patients.
An alkaloid, originally from Atropa belladonna, but found in other plants, mainly SOLANACEAE. Hyoscyamine is the 3(S)-endo isomer of atropine.
Diphenylacetic acids are organic compounds characterized by a structure containing two phenyl groups (aromatic rings) bonded to an acetic acid group, which have been used in pharmaceuticals and research due to their anti-inflammatory, antifungal, and muscle relaxant properties.
Drugs that bind to and activate cholinergic receptors.
Any drug used for its actions on cholinergic systems. Included here are agonists and antagonists, drugs that affect the life cycle of ACETYLCHOLINE, and drugs that affect the survival of cholinergic neurons. The term cholinergic agents is sometimes still used in the narrower sense of MUSCARINIC AGONISTS, although most modern texts discourage that usage.
A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.
Thiadiazoles are heterocyclic compounds containing a five-membered ring with two nitrogen atoms and two sulfur atoms, which have been widely studied for their potential therapeutic benefits, including antibacterial, antifungal, anti-inflammatory, and antitumor activities.
A toxic alkaloid found in Amanita muscaria (fly fungus) and other fungi of the Inocybe species. It is the first parasympathomimetic substance ever studied and causes profound parasympathetic activation that may end in convulsions and death. The specific antidote is atropine.
Dioxolanes are specific chemical compounds characterized by a saturated six-membered ring containing two oxygen atoms and two carbon atoms, often formed through the reaction between aldehydes or ketones and diols, and significant in pharmaceutical synthesis and organic chemistry.
An alkaloid from SOLANACEAE, especially DATURA and SCOPOLIA. Scopolamine and its quaternary derivatives act as antimuscarinics like ATROPINE, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in URINARY INCONTINENCE, in MOTION SICKNESS, as an antispasmodic, and as a mydriatic and cycloplegic.
Analogs or derivatives of scopolamine.
A family of hexahydropyridines.
Drugs that mimic the effects of parasympathetic nervous system activity. Included here are drugs that directly stimulate muscarinic receptors and drugs that potentiate cholinergic activity, usually by slowing the breakdown of acetylcholine (CHOLINESTERASE INHIBITORS). Drugs that stimulate both sympathetic and parasympathetic postganglionic neurons (GANGLIONIC STIMULANTS) are not included here.
A muscarinic antagonist used as an antispasmodic and in urinary incontinence. It has little effect on glandular secretion or the cardiovascular system. It does have some local anesthetic properties and is used in gastrointestinal, biliary, and urinary tract spasms.
A slowly hydrolyzing muscarinic agonist with no nicotinic effects. Bethanechol is generally used to increase smooth muscle tone, as in the GI tract following abdominal surgery or in urinary retention in the absence of obstruction. It may cause hypotension, HEART RATE changes, and BRONCHIAL SPASM.
A muscarinic antagonist that has effects in both the central and peripheral nervous systems. It has been used in the treatment of arteriosclerotic, idiopathic, and postencephalitic parkinsonism. It has also been used to alleviate extrapyramidal symptoms induced by phenothiazine derivatives and reserpine.
A non-hydrolyzed muscarinic agonist used as a research tool.
Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)
Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).
A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma.
A quaternary ammonium parasympathomimetic agent with the muscarinic actions of ACETYLCHOLINE. It is hydrolyzed by ACETYLCHOLINESTERASE at a considerably slower rate than ACETYLCHOLINE and is more resistant to hydrolysis by nonspecific CHOLINESTERASES so that its actions are more prolonged. It is used as a parasympathomimetic bronchoconstrictor agent and as a diagnostic aid for bronchial asthma. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1116)
CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.
A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.
An independent state consisting of three islands in the Mediterranean Sea, south of Sicily. Its capital is Valetta. The major island is Malta, the two smaller islands are Comino and Gozo. It was a Phoenician and Carthaginian colony, captured by the Romans in 218 B.C. It was overrun by Saracens in 870, taken by the Normans in 1090, and subsequently held by the French and later the British who allotted them a dominion government in 1921. It became a crown colony in 1933, achieving independence in 1964. The name possibly comes from a pre-Indoeuropean root mel, high, referring to its rocks, but a more picturesque origin derives the name from the Greek melitta or melissa, honey, with reference to its early fame for its honey production. (From Webster's New Geographical Dictionary, 1988, p719 & Room, Brewer's Dictionary of Names, 1992, p330)
The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
One of the MUSCARINIC ANTAGONISTS with pharmacologic action similar to ATROPINE and used mainly as an ophthalmic parasympatholytic or mydriatic.
Phenomena and pharmaceutics of compounds that selectively bind to a specific receptor and trigger a response. They mimic the action of endogenous biochemical molecules. Their effect can be countered by antagonists (DRUG ANTAGONISM).
Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.
The distal and narrowest portion of the SMALL INTESTINE, between the JEJUNUM and the ILEOCECAL VALVE of the LARGE INTESTINE.
Cholinesterase reactivator occurring in two interchangeable isomeric forms, syn and anti.
A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.
A family of heterotrimeric GTP-binding protein alpha subunits that activate TYPE C PHOSPHOLIPASES dependent signaling pathways. The Gq-G11 part of the name is also spelled Gq/G11.
The relationship between the dose of an administered drug and the response of the organism to the drug.
A centrally active muscarinic antagonist that has been used in the symptomatic treatment of PARKINSON DISEASE. Benztropine also inhibits the uptake of dopamine.
A family of heterotrimeric GTP-binding protein alpha subunits that were originally identified by their ability to inhibit ADENYLYL CYCLASES. Members of this family can couple to beta and gamma G-protein subunits that activate POTASSIUM CHANNELS. The Gi-Go part of the name is also spelled Gi/Go.
An indole-dione that is obtained by oxidation of indigo blue. It is a MONOAMINE OXIDASE INHIBITOR and high levels have been found in urine of PARKINSONISM patients.
One of the virulence factors produced by BORDETELLA PERTUSSIS. It is a multimeric protein composed of five subunits S1 - S5. S1 contains mono ADPribose transferase activity.
Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to the hexahydroxy alcohol, myo-inositol. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid, myo-inositol, and 2 moles of fatty acids.
A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.
A cholinesterase inhibitor that crosses the blood-brain barrier. Tacrine has been used to counter the effects of muscle relaxants, as a respiratory stimulant, and in the treatment of Alzheimer's disease and other central nervous system disorders.
A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research.
A set of BACTERIAL ADHESINS and TOXINS, BIOLOGICAL produced by BORDETELLA organisms that determine the pathogenesis of BORDETELLA INFECTIONS, such as WHOOPING COUGH. They include filamentous hemagglutinin; FIMBRIAE PROTEINS; pertactin; PERTUSSIS TOXIN; ADENYLATE CYCLASE TOXIN; dermonecrotic toxin; tracheal cytotoxin; Bordetella LIPOPOLYSACCHARIDES; and tracheal colonization factor.
The modification of the reactivity of ENZYMES by the binding of effectors to sites (ALLOSTERIC SITES) on the enzymes other than the substrate BINDING SITES.
Phosphoric acid esters of inositol. They include mono- and polyphosphoric acid esters, with the exception of inositol hexaphosphate which is PHYTIC ACID.
Guanosine 5'-(trihydrogen diphosphate), monoanhydride with phosphorothioic acid. A stable GTP analog which enjoys a variety of physiological actions such as stimulation of guanine nucleotide-binding proteins, phosphoinositide hydrolysis, cyclic AMP accumulation, and activation of specific proto-oncogenes.
Nerve fibers liberating acetylcholine at the synapse after an impulse.
The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.
An analog of benzilylcholine mustard. It is an alkylating nitrogen mustard analog that binds specifically and irreversibly to cholinergic muscarinic receptors and is used as an affinity label to isolate and study the receptors.
The chambers of the heart, to which the BLOOD returns from the circulation.
A family of inwardly-rectifying potassium channels that are activated by PERTUSSIS TOXIN sensitive G-PROTEIN-COUPLED RECEPTORS. GIRK potassium channels are primarily activated by the complex of GTP-BINDING PROTEIN BETA SUBUNITS and GTP-BINDING PROTEIN GAMMA SUBUNITS.
A large family of evolutionarily conserved proteins that function as negative regulators of HETEROTRIMERIC GTP-BINDING PROTEINS. RGS PROTEINS act by increasing the GTPase activity of the G alpha subunit of a heterotrimeric GTP-binding protein, causing it to revert to its inactive (GDP-bound) form.
Benzilates are organic compounds that contain the structure of benzil, characterized by two benzoyl groups (-COPh) bonded to a central carbon atom, and can be esters of benzilic acid with various alcohols.
An alkaloid obtained from the betel nut (Areca catechu), fruit of a palm tree. It is an agonist at both muscarinic and nicotinic acetylcholine receptors. It is used in the form of various salts as a ganglionic stimulant, a parasympathomimetic, and a vermifuge, especially in veterinary practice. It has been used as a euphoriant in the Pacific Islands.
The imide of phthalic acids.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
A phosphoinositide phospholipase C subtype that is primarily regulated by its association with HETEROTRIMERIC G-PROTEINS. It is structurally related to PHOSPHOLIPASE C DELTA with the addition of C-terminal extension of 400 residues.
Quinuclidines are organic compounds consisting of a tricyclic structure with a three-membered ring fused to a piperidine ring, often used as building blocks in the synthesis of pharmaceuticals and bioactive molecules.
A site on an enzyme which upon binding of a modulator, causes the enzyme to undergo a conformational change that may alter its catalytic or binding properties.
A group of compounds that are derivatives of beta-methylacetylcholine (methacholine).
A high-affinity muscarinic antagonist commonly used as a tool in animal and tissue studies.
Use of electric potential or currents to elicit biological responses.
Tritium is an isotope of hydrogen (specifically, hydrogen-3) that contains one proton and two neutrons in its nucleus, making it radioactive with a half-life of about 12.3 years, and is used in various applications including nuclear research, illumination, and dating techniques due to its low energy beta decay.
Cell surface proteins that bind acetylcholine with high affinity and trigger intracellular changes influencing the behavior of cells. Cholinergic receptors are divided into two major classes, muscarinic and nicotinic, based originally on their affinity for nicotine and muscarine. Each group is further subdivided based on pharmacology, location, mode of action, and/or molecular biology.
The craniosacral division of the autonomic nervous system. The cell bodies of the parasympathetic preganglionic fibers are in brain stem nuclei and in the sacral spinal cord. They synapse in cranial autonomic ganglia or in terminal ganglia near target organs. The parasympathetic nervous system generally acts to conserve resources and restore homeostasis, often with effects reciprocal to the sympathetic nervous system.
Benzopyrroles with the nitrogen at the number two carbon, in contrast to INDOLES which have the nitrogen adjacent to the six-membered ring.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.
Bethanechol compounds are parasympathomimetic agents that directly stimulate muscarinic receptors, primarily used to treat urinary retention and nonobstructive bladder dysfunction by increasing bladder contractility and decreasing post-void residual volume.
That phase of a muscle twitch during which a muscle returns to a resting position.
The rate dynamics in chemical or physical systems.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits.
Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
Intracellular messenger formed by the action of phospholipase C on phosphatidylinositol 4,5-bisphosphate, which is one of the phospholipids that make up the cell membrane. Inositol 1,4,5-trisphosphate is released into the cytoplasm where it releases calcium ions from internal stores within the cell's endoplasmic reticulum. These calcium ions stimulate the activity of B kinase or calmodulin.
A muscarinic antagonist that has been used to treat neuroleptic-induced parkinsonism. Benzetimide is the (-)-enantimorph of dexetimide.
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
Neurotransmitter receptors located on or near presynaptic terminals or varicosities. Presynaptic receptors which bind transmitter molecules released by the terminal itself are termed AUTORECEPTORS.
The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).
The simultaneous or sequential binding of multiple cell surface receptors to different ligands resulting in coordinated stimulation or suppression of signal transduction.
A cholinesterase inhibitor that is rapidly absorbed through membranes. It can be applied topically to the conjunctiva. It also can cross the blood-brain barrier and is used when central nervous system effects are desired, as in the treatment of severe anticholinergic toxicity.
Ganglia of the parasympathetic nervous system, including the ciliary, pterygopalatine, submandibular, and otic ganglia in the cranial region and intrinsic (terminal) ganglia associated with target organs in the thorax and abdomen.
An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 4.6.1.1.
The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
The hollow, muscular organ that maintains the circulation of the blood.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
Drugs that bind to but do not activate CHOLINERGIC RECEPTORS, thereby blocking the actions of ACETYLCHOLINE or cholinergic agonists.
Drugs that inhibit cholinesterases. The neurotransmitter ACETYLCHOLINE is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system.
Analogs and derivatives of atropine.
A musculomembranous sac along the URINARY TRACT. URINE flows from the KIDNEYS into the bladder via the ureters (URETER), and is held there until URINATION.
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
The action of a drug that may affect the activity, metabolism, or toxicity of another drug.
Potassium channels where the flow of K+ ions into the cell is greater than the outward flow.
A non-depolarizing skeletal muscle relaxant similar to TUBOCURARINE. It is used as an anesthesia adjuvant.
The shortest and widest portion of the SMALL INTESTINE adjacent to the PYLORUS of the STOMACH. It is named for having the length equal to about the width of 12 fingers.
Compounds containing the hexamethylenebis(trimethylammonium) cation. Members of this group frequently act as antihypertensive agents and selective ganglionic blocking agents.
Established cell cultures that have the potential to propagate indefinitely.
A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)
The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.
The process of cleaving a chemical compound by the addition of a molecule of water.
A muscarinic antagonist used as an antispasmodic, in some disorders of the gastrointestinal tract, and to reduce salivation with some anesthetics.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
The largest of the three pairs of SALIVARY GLANDS. They lie on the sides of the FACE immediately below and in front of the EAR.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
Drugs that bind to nicotinic cholinergic receptors (RECEPTORS, NICOTINIC) and block the actions of acetylcholine or cholinergic agonists. Nicotinic antagonists block synaptic transmission at autonomic ganglia, the skeletal neuromuscular junction, and at central nervous system nicotinic synapses.
Elements of limited time intervals, contributing to particular results or situations.
One of the centrally acting MUSCARINIC ANTAGONISTS used for treatment of PARKINSONIAN DISORDERS and drug-induced extrapyramidal movement disorders and as an antispasmodic.
Proteins prepared by recombinant DNA technology.
The discharge of saliva from the SALIVARY GLANDS that keeps the mouth tissues moist and aids in digestion.
Venoms from snakes of the family Elapidae, including cobras, kraits, mambas, coral, tiger, and Australian snakes. The venoms contain polypeptide toxins of various kinds, cytolytic, hemolytic, and neurotoxic factors, but fewer enzymes than viper or crotalid venoms. Many of the toxins have been characterized.
The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx).
A nicotinic antagonist that is well absorbed from the gastrointestinal tract and crosses the blood-brain barrier. Mecamylamine has been used as a ganglionic blocker in treating hypertension, but, like most ganglionic blockers, is more often used now as a research tool.
Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A nicotinic cholinergic antagonist often referred to as the prototypical ganglionic blocker. It is poorly absorbed from the gastrointestinal tract and does not cross the blood-brain barrier. It has been used for a variety of therapeutic purposes including hypertension but, like the other ganglionic blockers, it has been replaced by more specific drugs for most purposes, although it is widely used a research tool.
A cholinesterase inhibitor used in the treatment of myasthenia gravis and to reverse the effects of muscle relaxants such as gallamine and tubocurarine. Neostigmine, unlike PHYSOSTIGMINE, does not cross the blood-brain barrier.
Ganglia of the sympathetic nervous system including the paravertebral and the prevertebral ganglia. Among these are the sympathetic chain ganglia, the superior, middle, and inferior cervical ganglia, and the aorticorenal, celiac, and stellate ganglia.
An enzyme that catalyzes the formation of acetylcholine from acetyl-CoA and choline. EC 2.3.1.6.
N-methyl-8-azabicyclo[3.2.1]octanes best known for the ones found in PLANTS.
A sympathomimetic that acts mainly by causing release of NOREPINEPHRINE but also has direct agonist activity at some adrenergic receptors. It is most commonly used as a nasal vasoconstrictor and an appetite depressant.
The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
Symptom of overactive detrusor muscle of the URINARY BLADDER that contracts with abnormally high frequency and urgency. Overactive bladder is characterized by the frequent feeling of needing to urinate during the day, during the night, or both. URINARY INCONTINENCE may or may not be present.
An enzyme that catalyzes the hydrolysis of ACETYLCHOLINE to CHOLINE and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7.
The largest and uppermost of the paravertebral sympathetic ganglia.

Comparison of functional antagonism between isoproterenol and M2 muscarinic receptors in guinea pig ileum and trachea. (1/491)

The ability of the M2 muscarinic receptor to mediate an inhibition of the relaxant effects of forskolin and isoproterenol was investigated in guinea pig ileum and trachea. In some experiments, trachea was first treated with 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) mustard to inactivate M3 receptors. The contractile response to oxotremorine-M was measured subsequently in the presence of both histamine (10 microM) and isoproterenol (10 nM). Under these conditions, [[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5, 11-dihydro-6H-pyrido[2,3b]-[1,4]benzodiazepine-6-one (AF-DX 116) antagonized the contractile response to oxotremorine-M in a manner consistent with an M3 mechanism. However, when the same experiment was repeated using forskolin (4 microM) instead of isoproterenol, the response to oxotremorine-M exhibited greater potency and was antagonized by AF-DX 116 in a manner consistent with an M2 mechanism. We also measured the effects of pertussis toxin treatment on the ability of isoproterenol to inhibit the contraction elicited by a single concentration of either histamine (0.3 microM) or oxotremorine-M (40 nM) in both the ileum and trachea. Pertussis toxin treatment had no significant effect on the potency of isoproterenol for inhibiting histamine-induced contractions in the ileum and trachea. In contrast, pertussis toxin treatment enhanced the relaxant potency of isoproterenol against oxotremorine-M-induced contractions in the ileum but not in the trachea. Also, pertussis toxin treatment enhanced the relaxant potency of forskolin against oxotremorine-M-induced contractions in the ileum and trachea. We investigated the relaxant potency of isoproterenol when very low, equi-effective (i.e., 20-34% of maximal response) concentrations of either histamine or oxotremorine-M were used to elicit contraction. Under these conditions, isoproterenol exhibited greater relaxant potency against histamine in the ileum but exhibited similar relaxant potencies against histamine and oxotremorine-M in the trachea. Following 4-DAMP mustard treatment, a low concentration of oxotremorine-M (10 nM) had no contractile effect in either the ileum or trachea. Nevertheless, in 4-DAMP mustard-treated tissue, oxotremorine-M (10 nM) reduced the relaxant potency of isoproterenol against histamine-induced contractions in the ileum, but not in the trachea. We conclude that in the trachea the M2 receptor mediates an inhibition of the relaxant effects of forskolin, but not isoproterenol, and the decreased relaxant potency of isoproterenol against contractions elicited by a muscarinic agonist relative to histamine is not due to activation of M2 receptors but rather to the greater contractile stimulus mediated by the M3 receptor compared with the H1 histamine receptor.  (+info)

Mixed agonist-antagonist properties of clozapine at different human cloned muscarinic receptor subtypes expressed in Chinese hamster ovary cells. (2/491)

We recently reported that clozapine behaves as a partial agonist at the cloned human m4 muscarinic receptor subtype. In the present study, we investigated whether the drug could elicit similar effects at the cloned human m1, m2, and m3 muscarinic receptor subtypes expressed in the Chinese hamster ovary (CHO) cells. Clozapine elicited a concentration-dependent stimulation of [3H]inositol phosphates accumulation in CHO cells expressing either the m1 or the m3 receptor subtype. Moreover, clozapine inhibited forskolin-stimulated cyclic AMP accumulation and enhanced [35S] GTP gamma S binding to membrane G proteins in CHO cells expressing the m2 receptor. These agonist effects of clozapine were antagonized by atropine. The intrinsic activity of clozapine was lower than that of the full cholinergic agonist carbachol, and, when the compounds were combined, clozapine potently reduced the receptor responses to carbachol. These data indicate that clozapine behaves as a partial agonist at different muscarinic receptor subtypes and may provide new hints for understanding the receptor mechanisms underlying the antipsychotic efficacy of the drug.  (+info)

Selective activation of heterologously expressed G protein-gated K+ channels by M2 muscarinic receptors in rat sympathetic neurones. (3/491)

1. G protein-regulated inward rectifier K+ (GIRK) channels were over-expressed in dissociated rat superior cervical sympathetic (SCG) neurones by co-transfecting green fluorescent protein (GFP)-, GIRK1- and GIRK2-expressing plasmids using the biolistic technique. Membrane currents were subsequently recorded with whole-cell patch electrodes. 2. Co-transfected cells had larger Ba2+-sensitive inwardly rectifying currents and 13 mV more negative resting potentials (in 3 mM [K+]o) than non-transfected cells, or cells transfected with GIRK1 or GIRK2 alone. 3. Carbachol (CCh, 1-30 microM) increased the inwardly rectifying current in 70 % of GIRK1+ GIRK2-transfected cells by 261 +/- 53 % (n = 6, CCh 30 microM) at -120 mV, but had no effect in non-transfected cells or in cells transfected with GIRK1 or GIRK2 alone. Pertussis toxin prevented the effect of carbachol but had no effect on basal currents. 4. The effect of CCh was antagonized by 6 nM tripitramine but not by 100 nM pirenzepine, consistent with activation of endogenous M2 muscarinic acetylcholine receptors. 5. In contrast, inhibition of the voltage-activated Ca2+ current by CCh was antagonized by 100 nM pirenzepine but not by 6 nM tripitramine, indicating that it was mediated by M4 muscarinic acetylcholine receptors. 6. We conclude that endogenous M2 and M4 muscarinic receptors selectively couple to GIRK currents and Ca2+ currents respectively, with negligible cross-talk.  (+info)

M2 receptors in genito-urinary smooth muscle pathology. (4/491)

In vitro bladder contractions in response to cumulative carbachol doses were measured in the presence of selective muscarinic antagonists from rats which had their major pelvic ganglion bilaterally removed (denervation, DEN) or from rats in which the spinal cord was injured (SCI) via compression. DEN induced both hypertrophy (505+/-51 mg bladder weight) and a supersensitivity of the bladders to carbachol (EC50=0.7+/-0.1 uM). Some of the SCI rats regained the ability to void spontaneously (SPV). The bladders of these animals weighed 184+/-17 mg, significantly less than the bladders of non voiding rats (NV, 644+/-92 mg). The potency of carbachol was greater in bladder strips from NV SCI animals (EC50=0.54+/-0.1 uM) than either bladder strips from SPV SCI (EC50=0.93+/-0.3 microM), DEN or control (EC50=1.2+/-0.1 microM) animals. Antagonist affinities in control bladders for antagonism of carbachol induced contractions were consistent with M3 mediated contractions. Antagonist affinities in DEN bladders for 4-diphenlacetoxy-N-methylpiperidine methiodide (4-DAMP, 8.5) and para fluoro hexahydrosilodifenidol (p-F-HHSiD, 6.6); were consistent with M2 mediated contractions, although the methoctramine affinity (6.5) was consistent with M3 mediated contractions. p-F-HHSiD inhibited carbachol induced contraction with an affinity consistent with M2 receptors in bladders from NV SCI (pKb=6.4) animals and M3 receptors in bladders from SPV SCI animals (pKb=7.9). Subtype selective immunoprecipitation of muscarinic receptors revealed an increase in total and an increase in M2 receptor density with no change in M3 receptor density in bladders from DEN and NV SCI animals compared to normal or sham operated controls. M3 receptor density was lower in bladders from SPV SCI animals while the M2 receptor density was not different from control. This increase in M2 receptor density is consistent with the change in affinity of the antagonists for inhibition of carbachol induced contractions and may indicate that M2 receptors or a combination of M2 and M3 receptors directly mediate smooth muscle contraction in bladders from DEN and NV SCI rats.  (+info)

Muscarinic M3 receptor inactivation reveals a pertussis toxin-sensitive contractile response in the guinea pig colon: evidence for M2/M3 receptor interactions. (5/491)

The role of M2 and M3 receptors in the contractile and phosphoinositide responses elicited to oxotremorine-M was investigated in the guinea pig colon. Under standard conditions, both the contractile and phosphoinositide responses were insensitive to pertussis toxin and irreversibly antagonized by alkylation of M3 receptors with N-(2-chloroethyl)-4-piperidinyl diphenylacetate. After treatment with N-(2-chloroethyl)-4-piperidinyl diphenylacetate, the remaining contractile response was sensitive to pertussis toxin and weakly antagonized by the M2- and M4-selective antagonist AF-DX 116. In contrast, the residual phosphoinositide response was unaffected by pertussis toxin. The pertussis toxin sensitivity of the remaining contractile response suggests that the M2 receptor is mediating the contraction, whereas its weak antagonism by AF-DX 116 suggests that an alternate muscarinic subtype mediates the response. To explain this enigma, we investigated a mathematical model for receptor action based on an interaction between two receptor subtypes (M2 and M3). This model predicts that a response mediated by both the M2 and M3 receptor can be pertussis toxin sensitive yet exhibit an antagonistic profile indicative of an M3 response.  (+info)

Inverse agonist activity of pirenzepine at M2 muscarinic acetylcholine receptors. (6/491)

1. The intrinsic properties of muscarinic ligands were studied through their binding properties and their abilities to modulate the GTPase activity of G proteins coupled to muscarinic M2 receptors in pig atrial sarcolemma. 2. Competition binding experiments were performed with [3H]-oxotremorine-M to assess the affinity of receptors coupled to G proteins (R*), with [3H]-N-methylscopolamine ([3H]-NMS) to estimate the affinities of coupled and uncoupled receptors (R*+R) and with [3H]-NMS in the presence of GppNHp to assess the affinity of uncoupled receptors (R). 3. The ranking of Ki values for the agonist carbachol was R*<R*+R>R (174, 155, 115 nM), suggesting inverse agonism. 4. The Vmax of the basal high affinity GTPase activity of pig atrial sarcolemma was increased by mastoparan and decreased by GPAnt-2 indicating the relevance of this activity to G proteins coupled to receptors (R*). The K(M) value (0.26-0.33 microM) was not modified by mastoparan or GPAnt-2. 5. Carbachol increased the Vmax of GTP hydrolysis (EC50 8.1+/-0.3 microM), whereas atropine and AF-DX 116, up to 1 mM, did not modify it. Pirenzepine decreased the Vmax of GTP hydrolysis (EC50 77.5+/-10.3 microM). This effect was enhanced when KCI was substituted for NaCl (EC50 11.0+/-0.8 microM) and was antagonized by atropine and AF-DX 116 (IC50 0.91+/-0.71 and 197+/-85 nM). 6. Pirenzepine is proposed as an inverse agonist and atropine and AF-DX 116 as neutral antagonists at the muscarinic M2 receptor.  (+info)

Cholinergic modulation of neostriatal output: a functional antagonism between different types of muscarinic receptors. (7/491)

It is demonstrated that acetylcholine released from cholinergic interneurons modulates the excitability of neostriatal projection neurons. Physostigmine and neostigmine increase input resistance (RN) and enhance evoked discharge of spiny projection neurons in a manner similar to muscarine. Muscarinic RN increase occurs in the whole subthreshold voltage range (-100 to -45 mV), remains in the presence of TTX and Cd2+, and can be blocked by the relatively selective M1,4 muscarinic receptor antagonist pirenzepine but not by M2 or M3 selective antagonists. Cs+ occludes muscarinic effects at potentials more negative than -80 mV. A Na+ reduction in the bath occludes muscarinic effects at potentials more positive than -70 mV. Thus, muscarinic effects involve different ionic conductances: inward rectifying and cationic. The relatively selective M2 receptor antagonist AF-DX 116 does not block muscarinic effects on the projection neuron but, surprisingly, has the ability to mimic agonistic actions increasing RN and firing. Both effects are blocked by pirenzepine. HPLC measurements of acetylcholine demonstrate that AF-DX 116 but not pirenzepine greatly increases endogenous acetylcholine release in brain slices. Therefore, the effects of the M2 antagonist on the projection neurons were attributable to autoreceptor block on cholinergic interneurons. These experiments show distinct opposite functions of muscarinic M1- and M2-type receptors in neostriatal output, i.e., the firing of projection neurons. The results suggest that the use of more selective antimuscarinics may be more profitable for the treatment of motor deficits.  (+info)

G-protein coupled receptor kinases as modulators of G-protein signalling. (8/491)

G-protein coupled receptors (GPCRs) comprise one of the largest classes of signalling molecules. A wide diversity of activating ligands induce the active conformation of GPCRs and lead to signalling via heterotrimeric G-proteins and downstream effectors. In addition, a complex series of reactions participate in the 'turn-off' of GPCRs in both physiological and pharmacological settings. Some key players in the inactivation or 'desensitization' of GPCRs have been identified, whereas others remain the target of ongoing studies. G-protein coupled receptor kinases (GRKs) specifically phosphorylate activated GPCRs and initiate homologous desensitization. Uncoupling proteins, such as members of the arrestin family, bind to the phosphorylated and activated GPCRs and cause desensitization by precluding further interactions of the GPCRs and G-proteins. Adaptor proteins, including arrestins, and endocytic machinery participate in the internalization of GPCRs away from their normal signalling milieu. In this review we discuss the roles of these regulatory molecules as modulators of GPCR signalling.  (+info)

A muscarinic M3 receptor is a type of G protein-coupled receptor (GPCR) that binds to the neurotransmitter acetylcholine. It is a subtype of muscarinic receptors, which are named after the muscarine mushroom alkaloid that can activate them.

The M3 receptor is widely expressed in various tissues and organs, including the smooth muscle of the gastrointestinal tract, urinary bladder, respiratory system, and vasculature. When activated by acetylcholine or muscarinic agonists, it triggers a range of intracellular signaling pathways that lead to various physiological responses, such as smooth muscle contraction, glandular secretion, and modulation of neurotransmitter release.

The M3 receptor is known to couple primarily to the Gq/11 family of G proteins, which activate phospholipase C (PLC) and increase intracellular calcium levels. This leads to smooth muscle contraction and other downstream effects. The M3 receptor also interacts with other signaling pathways, such as those involving adenylyl cyclase, mitogen-activated protein kinases (MAPKs), and ion channels.

Dysregulation of muscarinic M3 receptors has been implicated in various diseases, including gastrointestinal disorders, overactive bladder syndrome, asthma, and cardiovascular diseases. Therefore, selective modulation of this receptor subtype is a potential therapeutic strategy for these conditions.

A muscarinic acetylcholine receptor (mAChR) is a type of G protein-coupled receptor (GPCR) that binds the neurotransmitter acetylcholine and mediates various responses in the body. The M1 subtype of muscarinic receptors (CHRM1) is widely distributed throughout the central and peripheral nervous system, with particularly high densities found in the cerebral cortex, hippocampus, striatum, and autonomic ganglia.

Muscarinic M1 receptors are coupled to G proteins of the Gq/11 family, which activate phospholipase C (PLC) upon receptor activation. This leads to the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol trisphosphate (IP3) and diacylglycerol (DAG), which further trigger intracellular signaling cascades.

The activation of muscarinic M1 receptors is involved in several physiological processes, including:

* Cognitive functions such as learning, memory, and attention
* Excitatory neurotransmission in the hippocampus
* Regulation of smooth muscle tone, particularly in the gastrointestinal tract and airways
* Secretion of various hormones and enzymes, including those involved in insulin release and lipid metabolism

Dysregulation of muscarinic M1 receptors has been implicated in several pathological conditions, such as Alzheimer's disease, Parkinson's disease, schizophrenia, and irritable bowel syndrome. Therefore, targeting these receptors with pharmacological agents presents a potential therapeutic strategy for treating these disorders.

Muscarinic receptors are a type of G protein-coupled receptor (GPCR) that bind to the neurotransmitter acetylcholine. They are found in various organ systems, including the nervous system, cardiovascular system, and respiratory system. Muscarinic receptors are activated by muscarine, a type of alkaloid found in certain mushrooms, and are classified into five subtypes (M1-M5) based on their pharmacological properties and signaling pathways.

Muscarinic receptors play an essential role in regulating various physiological functions, such as heart rate, smooth muscle contraction, glandular secretion, and cognitive processes. Activation of M1, M3, and M5 muscarinic receptors leads to the activation of phospholipase C (PLC) and the production of inositol trisphosphate (IP3) and diacylglycerol (DAG), which increase intracellular calcium levels and activate protein kinase C (PKC). Activation of M2 and M4 muscarinic receptors inhibits adenylyl cyclase, reducing the production of cAMP and modulating ion channel activity.

In summary, muscarinic receptors are a type of GPCR that binds to acetylcholine and regulates various physiological functions in different organ systems. They are classified into five subtypes based on their pharmacological properties and signaling pathways.

A muscarinic M2 receptor is a type of G protein-coupled receptor (GPCR) that binds to the neurotransmitter acetylcholine. It is one of five subtypes of muscarinic receptors (M1-M5) and is widely distributed throughout the body, particularly in the heart, smooth muscle, and exocrine glands.

The M2 receptor is coupled to the G protein inhibitory Gαi/o, which inhibits adenylyl cyclase activity and reduces intracellular cAMP levels. This leads to a variety of physiological responses, including negative chronotropy (slowing of heart rate) and negative inotropy (decreased contractility) in the heart, relaxation of smooth muscle in the bronchioles and gastrointestinal tract, and inhibition of exocrine gland secretion.

The M2 receptor is an important target for drugs used to treat a variety of conditions, including cardiovascular diseases, asthma, chronic obstructive pulmonary disease (COPD), and gastrointestinal disorders. Anticholinergic drugs such as atropine and ipratropium bind to the M2 receptor and block its activity, while muscarinic agonists such as bethanechol activate the receptor.

Muscarinic antagonists, also known as muscarinic receptor antagonists or parasympatholytics, are a class of drugs that block the action of acetylcholine at muscarinic receptors. Acetylcholine is a neurotransmitter that plays an important role in the parasympathetic nervous system, which helps to regulate various bodily functions such as heart rate, digestion, and respiration.

Muscarinic antagonists work by binding to muscarinic receptors, which are found in various organs throughout the body, including the eyes, lungs, heart, and gastrointestinal tract. By blocking the action of acetylcholine at these receptors, muscarinic antagonists can produce a range of effects depending on the specific receptor subtype that is affected.

For example, muscarinic antagonists may be used to treat conditions such as chronic obstructive pulmonary disease (COPD) and asthma by relaxing the smooth muscle in the airways and reducing bronchoconstriction. They may also be used to treat conditions such as urinary incontinence or overactive bladder by reducing bladder contractions.

Some common muscarinic antagonists include atropine, scopolamine, ipratropium, and tiotropium. It's important to note that these drugs can have significant side effects, including dry mouth, blurred vision, constipation, and confusion, especially when used in high doses or for prolonged periods of time.

Muscarinic agonists are a type of medication that binds to and activates muscarinic acetylcholine receptors, which are found in various organ systems throughout the body. These receptors are activated naturally by the neurotransmitter acetylcholine, and when muscarinic agonists bind to them, they mimic the effects of acetylcholine.

Muscarinic agonists can have a range of effects on different organ systems, depending on which receptors they activate. For example, they may cause bronchodilation (opening up of the airways) in the respiratory system, decreased heart rate and blood pressure in the cardiovascular system, increased glandular secretions in the gastrointestinal and salivary systems, and relaxation of smooth muscle in the urinary and reproductive systems.

Some examples of muscarinic agonists include pilocarpine, which is used to treat dry mouth and glaucoma, and bethanechol, which is used to treat urinary retention. It's important to note that muscarinic agonists can also have side effects, such as sweating, nausea, vomiting, and diarrhea, due to their activation of receptors in various organ systems.

A muscarinic receptor, M4 (also known as CHRM4 or cholinergic receptor, muscarinic 4) is a type of G protein-coupled receptor found in the cell membrane that responds to the neurotransmitter acetylcholine. It has been identified as one of five muscarinic receptor subtypes (M1-M5).

The M4 receptor is widely distributed throughout the body, particularly in the brain and certain peripheral organs such as the heart and lungs. In the central nervous system, M4 receptors are found to be highly expressed in areas like the striatum, hippocampus, and cortex.

The activation of M4 receptors primarily inhibits adenylyl cyclase activity via coupling with G proteins (Gαi/o), which leads to a decrease in intracellular cAMP levels. This results in the modulation of various cellular responses, including ion channel activity and second messenger cascades.

M4 receptors have been implicated in several physiological functions, such as learning, memory, cognition, emotion, and neuroprotection. In addition, they play a role in regulating the release of other neurotransmitters like dopamine, glutamate, and GABA. Dysregulation of M4 receptors has been associated with various neurological and psychiatric disorders, including Parkinson's disease, schizophrenia, and addiction.

N-Methylscopolamine is a anticholinergic drug, which means it blocks the action of acetylcholine, a neurotransmitter in the body. It is a derivative of scopolamine and is used to treat various conditions such as gastrointestinal disorders (such as gastritis, peptic ulcer), Parkinson's disease, motion sickness, and to reduce saliva production during surgical or diagnostic procedures.

It works by blocking the muscarinic receptors in the nervous system, which leads to a decrease in the secretion of fluids (such as saliva, sweat, stomach acid) and decreased muscle contractions in the gastrointestinal tract. N-Methylscopolamine can also cause side effects such as dizziness, dry mouth, blurred vision, and difficulty urinating.

A muscarinic acetylcholine receptor (mAChR) is a type of G protein-coupled receptor (GPCR) that binds the neurotransmitter acetylcholine and mediates various responses in the body. The M5 subtype of muscarinic receptors (CHRM5) is one of five subtypes (M1-M5) and is widely distributed throughout the body, including in the brain, smooth muscle, and exocrine glands.

Muscarinic M5 receptors are primarily expressed in the autonomic nervous system, where they play a role in regulating smooth muscle contraction, heart rate, and neurotransmitter release. They are also found in other tissues, such as the adrenal gland, where they modulate hormone secretion.

Muscarinic M5 receptors couple to G proteins of the Gq/11 family, which activate phospholipase C (PLC) and increase intracellular calcium levels upon activation. This leads to a variety of downstream effects, including smooth muscle contraction, increased heart rate, and altered neurotransmitter release.

In summary, muscarinic M5 receptors are a type of GPCR that binds acetylcholine and mediates various physiological responses in the body, particularly in the autonomic nervous system.

'Diamines' are organic compounds containing two amino groups (-NH2) in their molecular structure. The term 'diamine' itself does not have a specific medical definition, but it is used in the context of chemistry and biochemistry.

Diamines can be classified based on the number of carbon atoms between the two amino groups. For example, ethylenediamine and propylenediamine are diamines with one and two methylene (-CH2-) groups, respectively.

In medicine, certain diamines may have biological significance. For instance, putrescine and cadaverine are polyamines that are produced during the decomposition of animal tissues and can be found in necrotic or infected tissues. These compounds have been implicated in various pathological processes, including inflammation, oxidative stress, and cancer progression.

It is important to note that while some diamines may have medical relevance, the term 'diamines' itself does not have a specific medical definition.

Carbachol is a cholinergic agonist, which means it stimulates the parasympathetic nervous system by mimicking the action of acetylcholine, a neurotransmitter that is involved in transmitting signals between nerves and muscles. Carbachol binds to both muscarinic and nicotinic receptors, but its effects are more pronounced on muscarinic receptors.

Carbachol is used in medical treatments to produce miosis (pupil constriction), lower intraocular pressure, and stimulate gastrointestinal motility. It can also be used as a diagnostic tool to test for certain conditions such as Hirschsprung's disease.

Like any medication, carbachol can have side effects, including sweating, salivation, nausea, vomiting, diarrhea, bradycardia (slow heart rate), and bronchoconstriction (narrowing of the airways in the lungs). It should be used with caution and under the supervision of a healthcare professional.

Parasympatholytics are a type of medication that blocks the action of the parasympathetic nervous system. The parasympathetic nervous system is responsible for the body's rest and digest response, which includes slowing the heart rate, increasing intestinal and glandular activity, and promoting urination and defecation.

Parasympatholytics work by selectively binding to muscarinic receptors, which are found in various organs throughout the body, including the heart, lungs, and digestive system. By blocking these receptors, parasympatholytics can cause a range of effects, such as an increased heart rate, decreased glandular secretions, and reduced intestinal motility.

Some common examples of parasympatholytics include atropine, scopolamine, and ipratropium. These medications are often used to treat conditions such as bradycardia (slow heart rate), excessive salivation, and gastrointestinal cramping or diarrhea. However, because they can have significant side effects, parasympatholytics are typically used only when necessary and under the close supervision of a healthcare provider.

Gallamine triethiodide is not typically considered a medical term, but it is a pharmacological substance with historical use in anesthesia. It is a quaternary ammonium compound with muscarinic anticholinergic and skeletal muscle relaxant properties. The chemical formula for gallamine triethiodide is C17H24I3N2O2.

In a medical or clinical context, gallamine triethiodide has been used as an adjunct to general anesthesia to provide muscle relaxation during surgical procedures. However, due to its significant side effects and the availability of safer alternatives, it is no longer commonly used in modern anesthetic practice.

Pirenzepine is a medication that belongs to a class of drugs called anticholinergics or parasympatholytics. It works by blocking the action of acetylcholine, a neurotransmitter in the body, on certain types of muscarinic receptors.

Pirenzepine is primarily used to treat peptic ulcers and gastroesophageal reflux disease (GERD) by reducing the production of stomach acid. It may also be used to manage symptoms of irritable bowel syndrome, such as abdominal pain and diarrhea.

The medication is available in the form of tablets or gel for topical application. Side effects of pirenzepine may include dry mouth, blurred vision, constipation, dizziness, and difficulty urinating. It should be used with caution in people with glaucoma, benign prostatic hyperplasia, or other conditions that may be exacerbated by anticholinergic drugs.

It is important to note that this definition is for informational purposes only and should not be taken as medical advice. Always consult with a healthcare professional before starting any new medication.

Atropine is an anticholinergic drug that blocks the action of the neurotransmitter acetylcholine in the central and peripheral nervous system. It is derived from the belladonna alkaloids, which are found in plants such as deadly nightshade (Atropa belladonna), Jimson weed (Datura stramonium), and Duboisia spp.

In clinical medicine, atropine is used to reduce secretions, increase heart rate, and dilate the pupils. It is often used before surgery to dry up secretions in the mouth, throat, and lungs, and to reduce salivation during the procedure. Atropine is also used to treat certain types of nerve agent and pesticide poisoning, as well as to manage bradycardia (slow heart rate) and hypotension (low blood pressure) caused by beta-blockers or calcium channel blockers.

Atropine can have several side effects, including dry mouth, blurred vision, dizziness, confusion, and difficulty urinating. In high doses, it can cause delirium, hallucinations, and seizures. Atropine should be used with caution in patients with glaucoma, prostatic hypertrophy, or other conditions that may be exacerbated by its anticholinergic effects.

Diphenylacetic acids are a group of organic compounds characterized by the structure R-C6H4-COOH, where R represents a phenyl group (C6H5). These compounds contain two aromatic rings and an acidic functional group, making them diphenyl carboxylic acids. They can have various biological activities and are used in pharmaceuticals, agrochemicals, and other industrial applications. Some examples of diphenylacetic acids include:

1. Diphenylacetic acid (DPA): The simplest form of the compound with no substituents on either phenyl ring.
2. 2'-Hydroxy-diphenylacetic acid (HDPA): A derivative of diphenylacetic acid, containing a hydroxyl group (-OH) on one of the phenyl rings.
3. Diphenylacetic acid esters: Esters derived from diphenylacetic acids by reacting with alcohols, which can have various biological activities and are used in pharmaceuticals and agrochemicals.

It is important to note that specific medical definitions for 'diphenylacetic acids' may vary depending on the context and application.

Cholinergic agonists are substances that bind to and activate cholinergic receptors, which are neuroreceptors that respond to the neurotransmitter acetylcholine. These agents can mimic the effects of acetylcholine in the body and are used in medical treatment to produce effects such as pupil constriction, increased gastrointestinal motility, bronchodilation, and improved cognition. Examples of cholinergic agonists include pilocarpine, bethanechol, and donepezil.

Cholinergic agents are a class of drugs that mimic the action of acetylcholine, a neurotransmitter in the body that is involved in the transmission of nerve impulses. These agents work by either increasing the amount of acetylcholine in the synapse (the space between two neurons) or enhancing its action on receptors.

Cholinergic agents can be classified into two main categories: direct-acting and indirect-acting. Direct-acting cholinergic agents, also known as parasympathomimetics, directly stimulate muscarinic and nicotinic acetylcholine receptors. Examples of direct-acting cholinergic agents include pilocarpine, bethanechol, and carbamate.

Indirect-acting cholinergic agents, on the other hand, work by inhibiting the enzyme acetylcholinesterase, which is responsible for breaking down acetylcholine in the synapse. By inhibiting this enzyme, indirect-acting cholinergic agents increase the amount of acetylcholine available to stimulate receptors. Examples of indirect-acting cholinergic agents include physostigmine, neostigmine, and edrophonium.

Cholinergic agents are used in the treatment of a variety of medical conditions, including myasthenia gravis, Alzheimer's disease, glaucoma, and gastrointestinal disorders. However, they can also have significant side effects, such as bradycardia, bronchoconstriction, and increased salivation, due to their stimulation of muscarinic receptors. Therefore, they must be used with caution and under the close supervision of a healthcare provider.

Acetylcholine is a neurotransmitter, a type of chemical messenger that transmits signals across a chemical synapse from one neuron (nerve cell) to another "target" neuron, muscle cell, or gland cell. It is involved in both peripheral and central nervous system functions.

In the peripheral nervous system, acetylcholine acts as a neurotransmitter at the neuromuscular junction, where it transmits signals from motor neurons to activate muscles. Acetylcholine also acts as a neurotransmitter in the autonomic nervous system, where it is involved in both the sympathetic and parasympathetic systems.

In the central nervous system, acetylcholine plays a role in learning, memory, attention, and arousal. Disruptions in cholinergic neurotransmission have been implicated in several neurological disorders, including Alzheimer's disease, Parkinson's disease, and myasthenia gravis.

Acetylcholine is synthesized from choline and acetyl-CoA by the enzyme choline acetyltransferase and is stored in vesicles at the presynaptic terminal of the neuron. When a nerve impulse arrives, the vesicles fuse with the presynaptic membrane, releasing acetylcholine into the synapse. The acetylcholine then binds to receptors on the postsynaptic membrane, triggering a response in the target cell. Acetylcholine is subsequently degraded by the enzyme acetylcholinesterase, which terminates its action and allows for signal transduction to be repeated.

Thiadiazoles are heterocyclic compounds that contain a five-membered ring consisting of two nitrogen atoms and two sulfur atoms, along with a third non-carbon atom or group. They have the molecular formula N-S-N-C-S. Thiadiazole rings can be found in various pharmaceutical and agrochemical compounds, as they exhibit a wide range of biological activities, including anti-inflammatory, antimicrobial, antiviral, and anticancer properties. Some well-known thiadiazole derivatives include the drugs furazolidone, nitrofurantoin, and sufasalazine.

Muscarine is a naturally occurring organic compound that is classified as an alkaloid. It is found in various mushrooms, particularly those in the Amanita genus such as Amanita muscaria (the fly agaric) and Amanita pantherina. Muscarine acts as a parasympathomimetic, which means it can bind to and stimulate the same receptors as the neurotransmitter acetylcholine in the parasympathetic nervous system. This can lead to various effects on the body, including slowed heart rate, increased salivation, constricted pupils, and difficulty breathing. In high doses, muscarine can be toxic and even life-threatening.

Dioxolanes are a class of organic compounds that contain a five-membered ring consisting of two carbon atoms, one oxygen atom, and two adjacent oxygen or sulfur atoms. The general structure of dioxolane is C2O2S2 or C2O3. These compounds are often used in the synthesis of pharmaceuticals, agrochemicals, and other organic compounds due to their high reactivity and ability to act as protecting groups for carbonyl functionalities. Dioxolanes can also be found naturally in some foods and plants.

Scopolamine hydrobromide is a synthetic anticholinergic drug, which means it blocks the action of acetylcholine, a neurotransmitter in the nervous system. It is primarily used for its anti-motion sickness and anti-nausea effects. It can also be used to help with symptoms of Parkinson's disease, such as muscle stiffness and tremors.

In medical settings, scopolamine hydrobromide may be administered as a transdermal patch, which is placed behind the ear to allow for slow release into the body over several days. It can also be given as an injection or taken orally in the form of tablets or liquid solutions.

It's important to note that scopolamine hydrobromide can have various side effects, including dry mouth, blurred vision, dizziness, and drowsiness. It may also cause confusion, especially in older adults, and should be used with caution in patients with glaucoma, enlarged prostate, or certain heart conditions.

Scopolamine derivatives are a class of compounds that are chemically related to scopolamine, a natural alkaloid found in certain plants such as nightshade. These derivatives share similar structural and pharmacological properties with scopolamine, which is a muscarinic antagonist. They block the action of acetylcholine, a neurotransmitter, at muscarinic receptors in the nervous system.

Scopolamine derivatives are commonly used in medical settings as anticholinergics, which have various therapeutic applications. They can be used to treat conditions such as motion sickness, nausea and vomiting, Parkinson's disease, and certain types of nerve agent poisoning. Some examples of scopolamine derivatives include hyoscine, pirenzepine, and telenzepine.

It is important to note that scopolamine derivatives can have significant side effects, including dry mouth, blurred vision, dizziness, and cognitive impairment. Therefore, they should be used with caution and under the close supervision of a healthcare provider.

Piperidines are not a medical term per se, but they are a class of organic compounds that have important applications in the pharmaceutical industry. Medically relevant piperidines include various drugs such as some antihistamines, antidepressants, and muscle relaxants.

A piperidine is a heterocyclic amine with a six-membered ring containing five carbon atoms and one nitrogen atom. The structure can be described as a cyclic secondary amine. Piperidines are found in some natural alkaloids, such as those derived from the pepper plant (Piper nigrum), which gives piperidines their name.

In a medical context, it is more common to encounter specific drugs that belong to the class of piperidines rather than the term itself.

Parasympathomimetics are substances or drugs that mimic the actions of the parasympathetic nervous system. The parasympathetic nervous system is one of the two branches of the autonomic nervous system, which regulates involuntary physiological functions. It is responsible for the "rest and digest" response, and its neurotransmitter is acetylcholine.

Parasympathomimetic drugs work by either directly stimulating muscarinic receptors or increasing the availability of acetylcholine in the synaptic cleft. These drugs can have various effects on different organs, depending on the specific receptors they target. Some common effects include decreasing heart rate and contractility, reducing respiratory rate, constricting pupils, increasing glandular secretions (such as saliva and sweat), stimulating digestion, and promoting urination and defecation.

Examples of parasympathomimetic drugs include pilocarpine, which is used to treat dry mouth and glaucoma; bethanechol, which is used to treat urinary retention and neurogenic bladder; and neostigmine, which is used to treat myasthenia gravis and reverse the effects of non-depolarizing muscle relaxants.

Dicyclomine is an anticholinergic medication that is primarily used to treat gastrointestinal (GI) disorders such as irritable bowel syndrome (IBS). It works by blocking the action of acetylcholine, a neurotransmitter that stimulates muscle contraction and other functions in the body.

In the GI tract, dicyclomine helps to reduce spasms and relax the muscles, which can alleviate symptoms such as abdominal cramping, bloating, and diarrhea. It is important to note that dicyclomine may have side effects, including dry mouth, blurred vision, dizziness, and constipation.

Additionally, it should be used with caution in older adults, people with certain medical conditions (such as glaucoma or enlarged prostate), and those taking other medications that can interact with dicyclomine. Always consult with a healthcare provider for proper dosage and usage instructions.

Bethanechol is a parasympathomimetic drug, which means it stimulates the parasympathetic nervous system. This system is responsible for regulating many automatic functions in the body, including digestion and urination. Bethanechol works by causing the smooth muscles of the bladder to contract, which can help to promote urination in people who have difficulty emptying their bladder completely due to certain medical conditions such as surgery, spinal cord injury, or multiple sclerosis.

The medical definition of 'Bethanechol' is:

A parasympathomimetic agent that stimulates the muscarinic receptors of the autonomic nervous system, causing contraction of smooth muscle and increased secretion of exocrine glands. It is used to treat urinary retention and associated symptoms, such as those caused by bladder-neck obstruction due to prostatic hypertrophy or neurogenic bladder dysfunction. Bethanechol may also be used to diagnose urinary tract obstruction and to test the integrity of the bladder's innervation.

Biperiden is an anticholinergic drug, which is primarily used to treat symptoms of Parkinson's disease such as stiffness, tremors, spasms, and poor muscle control. It works by blocking the action of a certain natural substance (acetylcholine) in the body. Biperiden can also be used to treat related conditions such as drooling, loss of bladder control, and movement disorders caused by certain medications.

Biperiden may also be used for purposes not listed in its medical product label, as determined by a doctor. It is available in immediate-release and extended-release tablets and oral solution forms. Common side effects include dizziness, drowsiness, dry mouth, blurred vision, and difficulty urinating. Serious side effects are rare but may include hallucinations, irregular heartbeat, and mental/mood changes.

It is important to follow the instructions of a healthcare professional when taking biperiden, as it can interact with other medications and have potentially serious side effects if not used properly.

Oxotremorine is a muscarinic receptor agonist, which means it binds to and activates muscarinic acetylcholine receptors. These receptors are found in the central and peripheral nervous system and are involved in various physiological functions, including cognition, motivation, reward, motor control, and sensory processing.

Oxotremorine is primarily used in research settings to study the role of muscarinic receptors in different physiological processes and diseases. It has been shown to produce effects similar to those caused by natural neurotransmitter acetylcholine, such as increased salivation, sweating, and gastrointestinal motility.

In addition, oxotremorine has been investigated for its potential therapeutic use in the treatment of various neurological disorders, including Alzheimer's disease, Parkinson's disease, and schizophrenia. However, its clinical use is limited due to its side effects, such as nausea, vomiting, diarrhea, and abdominal cramps.

Smooth muscle, also known as involuntary muscle, is a type of muscle that is controlled by the autonomic nervous system and functions without conscious effort. These muscles are found in the walls of hollow organs such as the stomach, intestines, bladder, and blood vessels, as well as in the eyes, skin, and other areas of the body.

Smooth muscle fibers are shorter and narrower than skeletal muscle fibers and do not have striations or sarcomeres, which give skeletal muscle its striped appearance. Smooth muscle is controlled by the autonomic nervous system through the release of neurotransmitters such as acetylcholine and norepinephrine, which bind to receptors on the smooth muscle cells and cause them to contract or relax.

Smooth muscle plays an important role in many physiological processes, including digestion, circulation, respiration, and elimination. It can also contribute to various medical conditions, such as hypertension, gastrointestinal disorders, and genitourinary dysfunction, when it becomes overactive or underactive.

A radioligand assay is a type of in vitro binding assay used in molecular biology and pharmacology to measure the affinity and quantity of a ligand (such as a drug or hormone) to its specific receptor. In this technique, a small amount of a radioactively labeled ligand, also known as a radioligand, is introduced to a sample containing the receptor of interest. The radioligand binds competitively with other unlabeled ligands present in the sample for the same binding site on the receptor. After allowing sufficient time for binding, the reaction is stopped, and the amount of bound radioligand is measured using a technique such as scintillation counting. The data obtained from this assay can be used to determine the dissociation constant (Kd) and maximum binding capacity (Bmax) of the receptor-ligand interaction, which are important parameters in understanding the pharmacological properties of drugs and other ligands.

Pilocarpine is a cholinergic agonist, which means it stimulates the parasympathetic nervous system by binding to muscarinic receptors. It is primarily used in the treatment of dry mouth (xerostomia) caused by radiation therapy or Sjögren's syndrome, as well as in the management of glaucoma due to its ability to construct the pupils and reduce intraocular pressure. Pilocarpine can also be used to treat certain cardiovascular conditions and chronic bronchitis. It is available in various forms, including tablets, ophthalmic solutions, and topical gels.

Methacholine chloride is a medication that is used as a diagnostic tool to help identify and assess the severity of asthma or other respiratory conditions that cause airway hyperresponsiveness. It is a synthetic derivative of acetylcholine, which is a neurotransmitter that causes smooth muscle contraction in the body.

When methacholine chloride is inhaled, it stimulates the muscarinic receptors in the airways, causing them to constrict or narrow. This response is measured and used to determine the degree of airway hyperresponsiveness, which can help diagnose asthma and assess its severity.

The methacholine challenge test involves inhaling progressively higher doses of methacholine chloride until a significant decrease in lung function is observed or until a maximum dose is reached. The test results are then used to guide treatment decisions and monitor the effectiveness of therapy. It's important to note that this test should be conducted under the supervision of a healthcare professional, as it carries some risks, including bronchoconstriction and respiratory distress.

CHO cells, or Chinese Hamster Ovary cells, are a type of immortalized cell line that are commonly used in scientific research and biotechnology. They were originally derived from the ovaries of a female Chinese hamster (Cricetulus griseus) in the 1950s.

CHO cells have several characteristics that make them useful for laboratory experiments. They can grow and divide indefinitely under appropriate conditions, which allows researchers to culture large quantities of them for study. Additionally, CHO cells are capable of expressing high levels of recombinant proteins, making them a popular choice for the production of therapeutic drugs, vaccines, and other biologics.

In particular, CHO cells have become a workhorse in the field of biotherapeutics, with many approved monoclonal antibody-based therapies being produced using these cells. The ability to genetically modify CHO cells through various methods has further expanded their utility in research and industrial applications.

It is important to note that while CHO cells are widely used in scientific research, they may not always accurately represent human cell behavior or respond to drugs and other compounds in the same way as human cells do. Therefore, results obtained using CHO cells should be validated in more relevant systems when possible.

I must clarify that the term "Guinea Pigs" is not typically used in medical definitions. However, in colloquial or informal language, it may refer to people who are used as the first to try out a new medical treatment or drug. This is known as being a "test subject" or "in a clinical trial."

In the field of scientific research, particularly in studies involving animals, guinea pigs are small rodents that are often used as experimental subjects due to their size, cost-effectiveness, and ease of handling. They are not actually pigs from Guinea, despite their name's origins being unclear. However, they do not exactly fit the description of being used in human medical experiments.

I'm sorry for any confusion, but "Malta" is not a medical term. It is a country located in Southern Europe, consisting of an archipelago in the Mediterranean Sea. If you have any questions about medical terminology or concepts, I would be happy to help with those!

The trachea, also known as the windpipe, is a tube-like structure in the respiratory system that connects the larynx (voice box) to the bronchi (the two branches leading to each lung). It is composed of several incomplete rings of cartilage and smooth muscle, which provide support and flexibility. The trachea plays a crucial role in directing incoming air to the lungs during inspiration and outgoing air to the larynx during expiration.

Cricetinae is a subfamily of rodents that includes hamsters, gerbils, and relatives. These small mammals are characterized by having short limbs, compact bodies, and cheek pouches for storing food. They are native to various parts of the world, particularly in Europe, Asia, and Africa. Some species are popular pets due to their small size, easy care, and friendly nature. In a medical context, understanding the biology and behavior of Cricetinae species can be important for individuals who keep them as pets or for researchers studying their physiology.

Tropicamide is a muscarinic antagonist, which is a type of drug that blocks the action of acetylcholine in the body. In particular, it blocks the muscarinic receptors found in the eye, which results in pupil dilation (mydriasis) and paralysis of the ciliary muscle (cycloplegia).

Tropicamide is commonly used in ophthalmology as a diagnostic aid during eye examinations. It is often instilled into the eye to dilate the pupil, which allows the eye care professional to more easily examine the back of the eye and assess conditions such as cataracts, glaucoma, or retinal disorders. The cycloplegic effect of tropicamide also helps to relax the accommodation reflex, making it easier to measure the refractive error of the eye and determine the appropriate prescription for eyeglasses or contact lenses.

It is important to note that tropicamide can cause temporary blurring of vision and sensitivity to light, so patients should be advised not to drive or operate heavy machinery until the effects of the medication have worn off.

Drug agonism is a concept in pharmacology that refers to the ability of a drug to bind to and activate a specific receptor in the body, leading to a physiological response. When a drug agonist binds to its target receptor, it causes a conformational change in the receptor's structure, which activates a signaling pathway that ultimately leads to a biological response.

The strength of the interaction between the drug and the receptor is often described in terms of affinity and efficacy. Affinity refers to the ability of the drug to bind to the receptor, while efficacy refers to the drug's ability to activate the receptor and cause a response. A full agonist has both high affinity and high efficacy for its target receptor, meaning that it can fully activate the receptor and produce a maximal response.

Partial agonists, on the other hand, have lower efficacy than full agonists, meaning that they can only partially activate the receptor and produce a submaximal response. Antagonists, in contrast, bind to the receptor without activating it, thereby blocking the effects of both full and partial agonists.

Understanding drug agonism is important for developing drugs with desired therapeutic effects while minimizing unwanted side effects. By carefully selecting drugs that target specific receptors with known affinity and efficacy profiles, researchers can design more effective treatments for a wide range of medical conditions.

GTP-binding proteins, also known as G proteins, are a family of molecular switches present in many organisms, including humans. They play a crucial role in signal transduction pathways, particularly those involved in cellular responses to external stimuli such as hormones, neurotransmitters, and sensory signals like light and odorants.

G proteins are composed of three subunits: α, β, and γ. The α-subunit binds GTP (guanosine triphosphate) and acts as the active component of the complex. When a G protein-coupled receptor (GPCR) is activated by an external signal, it triggers a conformational change in the associated G protein, allowing the α-subunit to exchange GDP (guanosine diphosphate) for GTP. This activation leads to dissociation of the G protein complex into the GTP-bound α-subunit and the βγ-subunit pair. Both the α-GTP and βγ subunits can then interact with downstream effectors, such as enzymes or ion channels, to propagate and amplify the signal within the cell.

The intrinsic GTPase activity of the α-subunit eventually hydrolyzes the bound GTP to GDP, which leads to re-association of the α and βγ subunits and termination of the signal. This cycle of activation and inactivation makes G proteins versatile signaling elements that can respond quickly and precisely to changing environmental conditions.

Defects in G protein-mediated signaling pathways have been implicated in various diseases, including cancer, neurological disorders, and cardiovascular diseases. Therefore, understanding the function and regulation of GTP-binding proteins is essential for developing targeted therapeutic strategies.

The ileum is the third and final segment of the small intestine, located between the jejunum and the cecum (the beginning of the large intestine). It plays a crucial role in nutrient absorption, particularly for vitamin B12 and bile salts. The ileum is characterized by its thin, lined walls and the presence of Peyer's patches, which are part of the immune system and help surveil for pathogens.

Obidoxime chloride is a medication that belongs to the class of drugs known as oximes. It is used as an antidote for nerve agent and organophosphate poisoning. Obidoxime works by reactivating the inhibited acetylcholinesterase enzyme, which is essential for normal functioning of the nervous system. This enzyme can be inhibited by nerve agents and organophosphates, leading to an overstimulation of the nervous system that can result in symptoms such as muscle weakness, seizures, respiratory failure, and death.

Obidoxime is administered intravenously and works by breaking down the bond between the nerve agent or organophosphate and the acetylcholinesterase enzyme, allowing the enzyme to function normally again. It is important to note that obidoxime should be administered as soon as possible after exposure to a nerve agent or organophosphate in order to be effective.

It's important to mention that Obidoxime Chloride is not used frequently and only in specific situations, it requires medical supervision and administration by trained healthcare professionals.

Muscle contraction is the physiological process in which muscle fibers shorten and generate force, leading to movement or stability of a body part. This process involves the sliding filament theory where thick and thin filaments within the sarcomeres (the functional units of muscles) slide past each other, facilitated by the interaction between myosin heads and actin filaments. The energy required for this action is provided by the hydrolysis of adenosine triphosphate (ATP). Muscle contractions can be voluntary or involuntary, and they play a crucial role in various bodily functions such as locomotion, circulation, respiration, and posture maintenance.

GTP-binding protein alpha subunits, Gq-G11, are a family of heterotrimeric G proteins that play a crucial role in intracellular signaling transduction pathways. They are composed of three subunits: alpha, beta, and gamma. The alpha subunit of this family is referred to as Gαq, Gα11, Gα14, or Gα15/16, depending on the specific type.

These G proteins are activated by G protein-coupled receptors (GPCRs) upon binding of an agonist to the receptor. The activation leads to the exchange of GDP for GTP on the alpha subunit, causing it to dissociate from the beta and gamma subunits and further interact with downstream effector proteins. This interaction ultimately results in the activation of various signaling cascades, including the phospholipase C beta (PLCβ) pathway, which leads to the production of second messengers such as inositol trisphosphate (IP3) and diacylglycerol (DAG), and subsequently calcium mobilization.

Defects or mutations in GTP-binding protein alpha subunits, Gq-G11, have been implicated in several diseases, such as cancer, cardiovascular disorders, and neurological conditions.

A dose-response relationship in the context of drugs refers to the changes in the effects or symptoms that occur as the dose of a drug is increased or decreased. Generally, as the dose of a drug is increased, the severity or intensity of its effects also increases. Conversely, as the dose is decreased, the effects of the drug become less severe or may disappear altogether.

The dose-response relationship is an important concept in pharmacology and toxicology because it helps to establish the safe and effective dosage range for a drug. By understanding how changes in the dose of a drug affect its therapeutic and adverse effects, healthcare providers can optimize treatment plans for their patients while minimizing the risk of harm.

The dose-response relationship is typically depicted as a curve that shows the relationship between the dose of a drug and its effect. The shape of the curve may vary depending on the drug and the specific effect being measured. Some drugs may have a steep dose-response curve, meaning that small changes in the dose can result in large differences in the effect. Other drugs may have a more gradual dose-response curve, where larger changes in the dose are needed to produce significant effects.

In addition to helping establish safe and effective dosages, the dose-response relationship is also used to evaluate the potential therapeutic benefits and risks of new drugs during clinical trials. By systematically testing different doses of a drug in controlled studies, researchers can identify the optimal dosage range for the drug and assess its safety and efficacy.

Benztropine is an anticholinergic medication that is primarily used to treat the symptoms of Parkinson's disease, such as rigidity, tremors, and muscle spasms. It works by blocking the action of acetylcholine, a neurotransmitter in the brain that is involved in the regulation of motor function.

Benztropine is also used to treat side effects caused by certain medications, such as antipsychotics, that can cause Parkinson-like symptoms. It may be prescribed to help reduce drooling or to manage muscle stiffness and restlessness.

The medication comes in the form of tablets or a solution for injection and is typically taken orally once or twice a day. Common side effects of benztropine include dry mouth, blurred vision, dizziness, and constipation. More serious side effects may include hallucinations, confusion, and irregular heartbeat.

It's important to note that benztropine can interact with other medications, so it's essential to inform your healthcare provider of all the drugs you are taking before starting this medication. Additionally, benztropine should be used cautiously in older adults, people with glaucoma or enlarged prostate, and those with a history of heart problems.

GTP-binding protein alpha subunits, Gi-Go, are a type of heterotrimeric G proteins that play a crucial role in signal transduction pathways associated with many hormones and neurotransmitters. These G proteins are composed of three subunits: alpha, beta, and gamma. The "Gi-Go" specifically refers to the alpha subunit of these G proteins, which can exist in two isoforms, Gi and Go.

When a G protein-coupled receptor (GPCR) is activated by an agonist, it undergoes a conformational change that allows it to act as a guanine nucleotide exchange factor (GEF). The GEF activity of the GPCR promotes the exchange of GDP for GTP on the alpha subunit of the heterotrimeric G protein. Once GTP is bound, the alpha subunit dissociates from the beta-gamma dimer and can then interact with downstream effectors to modulate various cellular responses.

The Gi-Go alpha subunits are inhibitory in nature, meaning that they typically inhibit the activity of adenylyl cyclase, an enzyme responsible for converting ATP to cAMP. This reduction in cAMP levels can have downstream effects on various cellular processes, such as gene transcription, ion channel regulation, and metabolic pathways.

In summary, GTP-binding protein alpha subunits, Gi-Go, are heterotrimeric G proteins that play an essential role in signal transduction pathways by modulating adenylyl cyclase activity upon GPCR activation, ultimately influencing various cellular responses through cAMP regulation.

Isatin is not a medical term, but rather an organic compound that has been used in various biochemical and medicinal research contexts. Here's the chemical definition:

Isatin, also known as indole-2,3-dione, is an organic compound with the formula C8H5NO2. It is a derivative of indole and consists of a benzene ring fused to a pyrrole ring, with two ketone functional groups (=O) at positions 2 and 3. Isatin is a white crystalline solid that is slightly soluble in water and more soluble in organic solvents. It occurs naturally in some plants and animals and can be synthesized in the laboratory.

In medical and biochemical research, isatin has been studied for its potential role as an inhibitor of various enzymes and biological targets, including monoamine oxidases, tyrosinase, and carbonic anhydrase. Some isatin derivatives have shown promising results in preclinical studies for the treatment of various diseases, such as cancer, neurodegenerative disorders, and infectious diseases. However, more research is needed to determine their safety and efficacy in humans before they can be approved for medical use.

Pertussis toxin is an exotoxin produced by the bacterium Bordetella pertussis, which is responsible for causing whooping cough in humans. This toxin has several effects on the host organism, including:

1. Adenylyl cyclase activation: Pertussis toxin enters the host cell and modifies a specific G protein (Gαi), leading to the continuous activation of adenylyl cyclase. This results in increased levels of intracellular cAMP, which disrupts various cellular processes.
2. Inhibition of immune response: Pertussis toxin impairs the host's immune response by inhibiting the migration and function of immune cells like neutrophils and macrophages. It also interferes with antigen presentation and T-cell activation, making it difficult for the body to clear the infection.
3. Increased inflammation: The continuous activation of adenylyl cyclase by pertussis toxin leads to increased production of proinflammatory cytokines, contributing to the severe coughing fits and other symptoms associated with whooping cough.

Pertussis toxin is an essential virulence factor for Bordetella pertussis, and its effects contribute significantly to the pathogenesis of whooping cough. Vaccination against pertussis includes inactivated or genetically detoxified forms of pertussis toxin, which provide immunity without causing disease symptoms.

Phosphatidylinositols (PIs) are a type of phospholipid that are abundant in the cell membrane. They contain a glycerol backbone, two fatty acid chains, and a head group consisting of myo-inositol, a cyclic sugar molecule, linked to a phosphate group.

Phosphatidylinositols can be phosphorylated at one or more of the hydroxyl groups on the inositol ring, forming various phosphoinositides (PtdInsPs) with different functions. These signaling molecules play crucial roles in regulating cellular processes such as membrane trafficking, cytoskeletal organization, and signal transduction pathways that control cell growth, differentiation, and survival.

Phosphatidylinositol 4,5-bisphosphate (PIP2) is a prominent phosphoinositide involved in the regulation of ion channels, enzymes, and cytoskeletal proteins. Upon activation of certain receptors, PIP2 can be cleaved by the enzyme phospholipase C into diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (InsP3), which act as second messengers to trigger downstream signaling events.

Type C phospholipases, also known as group CIA phospholipases or patatin-like phospholipase domain containing proteins (PNPLAs), are a subclass of phospholipases that specifically hydrolyze the sn-2 ester bond of glycerophospholipids. They belong to the PNPLA family, which includes nine members (PNPLA1-9) with diverse functions in lipid metabolism and cell signaling.

Type C phospholipases contain a patatin domain, which is a conserved region of approximately 240 amino acids that exhibits lipase and acyltransferase activities. These enzymes are primarily involved in the regulation of triglyceride metabolism, membrane remodeling, and cell signaling pathways.

PNPLA1 (adiponutrin) is mainly expressed in the liver and adipose tissue, where it plays a role in lipid droplet homeostasis and triglyceride hydrolysis. PNPLA2 (ATGL or desnutrin) is a key regulator of triglyceride metabolism, responsible for the initial step of triacylglycerol hydrolysis in adipose tissue and other tissues.

PNPLA3 (calcium-independent phospholipase A2 epsilon or iPLA2ε) is involved in membrane remodeling, arachidonic acid release, and cell signaling pathways. Mutations in PNPLA3 have been associated with an increased risk of developing nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease, and hepatic steatosis.

PNPLA4 (lipase maturation factor 1 or LMF1) is involved in the intracellular processing and trafficking of lipases, such as pancreatic lipase and hepatic lipase. PNPLA5 ( Mozart1 or GSPML) has been implicated in membrane trafficking and cell signaling pathways.

PNPLA6 (neuropathy target esterase or NTE) is primarily expressed in the brain, where it plays a role in maintaining neuronal integrity by regulating lipid metabolism. Mutations in PNPLA6 have been associated with neuropathy and cognitive impairment.

PNPLA7 (adiponutrin or ADPN) has been implicated in lipid droplet formation, triacylglycerol hydrolysis, and cell signaling pathways. Mutations in PNPLA7 have been associated with an increased risk of developing NAFLD and hepatic steatosis.

PNPLA8 (diglyceride lipase or DGLα) is involved in the regulation of intracellular triacylglycerol metabolism, particularly in adipocytes and muscle cells. PNPLA9 (calcium-independent phospholipase A2 gamma or iPLA2γ) has been implicated in membrane remodeling, arachidonic acid release, and cell signaling pathways.

PNPLA10 (calcium-independent phospholipase A2 delta or iPLA2δ) is involved in the regulation of intracellular triacylglycerol metabolism, particularly in adipocytes and muscle cells. PNPLA11 (calcium-independent phospholipase A2 epsilon or iPLA2ε) has been implicated in membrane remodeling, arachidonic acid release, and cell signaling pathways.

PNPLA12 (calcium-independent phospholipase A2 zeta or iPLA2ζ) is involved in the regulation of intracellular triacylglycerol metabolism, particularly in adipocytes and muscle cells. PNPLA13 (calcium-independent phospholipase A2 eta or iPLA2η) has been implicated in membrane remodeling, arachidonic acid release, and cell signaling pathways.

PNPLA14 (calcium-independent phospholipase A2 theta or iPLA2θ) is involved in the regulation of intracellular triacylglycerol metabolism, particularly in adipocytes and muscle cells. PNPLA15 (calcium-independent phospholipase A2 iota or iPLA2ι) has been implicated in membrane remodeling, arachidonic acid release, and cell signaling pathways.

PNPLA16 (calcium-independent phospholipase A2 kappa or iPLA2κ) is involved in the regulation of intracellular triacylglycerol metabolism, particularly in adipocytes and muscle cells. PNPLA17 (calcium-independent phospholipase A2 lambda or iPLA2λ) has been implicated in membrane remodeling, arachidonic acid release, and cell signaling pathways.

PNPLA18 (calcium-independent phospholipase A2 mu or iPLA2μ) is involved in the regulation of intracellular triacylglycerol metabolism, particularly in adipocytes and muscle cells. PNPLA19 (calcium-independent phospholipase A2 nu or iPLA2ν) has been implicated in membrane remodeling, arachidonic acid release, and cell signaling pathways.

PNPLA20 (calcium-independent phospholipase A2 xi or iPLA2ξ) is involved in the regulation of intracellular triacylglycerol metabolism, particularly in adipocytes and muscle cells. PNPLA21 (calcium-independent phospholipase A2 omicron or iPLA2ο) has been implicated in membrane remodeling, arachidonic acid release, and cell signaling pathways.

PNPLA22 (calcium-independent phospholipase A2 pi or iPLA2π) is involved in the regulation of intracellular triacylglycerol metabolism, particularly in adipocytes and muscle cells. PNPLA23 (calcium-independent phospholipase A2 rho or iPLA2ρ) has been implicated in membrane remodeling, arachidonic acid release, and cell signaling pathways.

PNPLA24 (calcium-independent phospholipase A2 sigma or iPLA2σ) is involved in the regulation of intracellular triacylglycerol metabolism, particularly in adipocytes and muscle cells. PNPLA25 (calcium-independent phospholipase A2 tau or iPLA2τ) has been implicated in membrane remodeling, arachidonic acid release, and cell signaling pathways.

PNPLA26 (calcium-independent phospholipase A2 upsilon or iPLA2υ) is involved in the regulation of intracellular triacylglycerol metabolism, particularly in adipocytes and muscle cells. PNPLA27 (calcium-independent phospholipase A2 phi or iPLA2φ) has been implicated in membrane remodeling, arachidonic acid release, and cell signaling pathways.

PNPLA28 (calcium-independent phospholipase A2 chi or iPLA2χ) is involved in the regulation of intracellular triacylglycerol metabolism, particularly in adipocytes and muscle cells. PNPLA29 (calcium-independent phospholipase A2 psi or iPLA2ψ) has been implicated in membrane remodeling, arachidonic acid release, and cell signaling pathways.

PNPLA30 (calcium-independent phospholipase A2 omega or iPLA2ω) is involved in the regulation of intracellular triacylglycerol metabolism, particularly in adipocytes and muscle cells. PNPLA31 (calcium-independent phospholipase A2 pi or iPLA2π) has been implicated in membrane remodeling, arachidonic acid release, and cell signaling pathways.

PNPLA32 (calcium-independent phospholipase A2 rho or iPLA2ρ) is involved in the regulation of intracellular triacylglycerol metabolism, particularly in adipocytes and muscle cells. PNPLA33 (calcium-independent phospholipase A2 sigma or iPLA2σ) has been implicated in membrane remodeling, ar

Tacrine is a parasympathomimetic alkaloid, which was used in the treatment of Alzheimer's disease. It works by increasing the levels of acetylcholine, a neurotransmitter in the brain that is important for memory and thinking. Tacrine was an inhibitor of acetylcholinesterase, the enzyme responsible for breaking down acetylcholine.

However, due to its significant hepatotoxicity (liver toxicity) and limited efficacy, tacrine is rarely used today. Other cholinesterase inhibitors, such as donepezil, rivastigmine, and galantamine, have largely replaced tacrine in the treatment of Alzheimer's disease.

"Cricetulus" is a genus of rodents that includes several species of hamsters. These small, burrowing animals are native to Asia and have a body length of about 8-15 centimeters, with a tail that is usually shorter than the body. They are characterized by their large cheek pouches, which they use to store food. Some common species in this genus include the Chinese hamster (Cricetulus griseus) and the Daurian hamster (Cricetulus dauuricus). These animals are often kept as pets or used in laboratory research.

Virulence factors in Bordetella pertussis, the bacterium that causes whooping cough, refer to the characteristics or components of the organism that contribute to its ability to cause disease. These virulence factors include:

1. Pertussis Toxin (PT): A protein exotoxin that inhibits the immune response and affects the nervous system, leading to the characteristic paroxysmal cough of whooping cough.
2. Adenylate Cyclase Toxin (ACT): A toxin that increases the levels of cAMP in host cells, disrupting their function and contributing to the pathogenesis of the disease.
3. Filamentous Hemagglutinin (FHA): A surface protein that allows the bacterium to adhere to host cells and evade the immune response.
4. Fimbriae: Hair-like appendages on the surface of the bacterium that facilitate adherence to host cells.
5. Pertactin (PRN): A surface protein that also contributes to adherence and is a common component of acellular pertussis vaccines.
6. Dermonecrotic Toxin: A toxin that causes localized tissue damage and necrosis, contributing to the inflammation and symptoms of whooping cough.
7. Tracheal Cytotoxin: A toxin that damages ciliated epithelial cells in the respiratory tract, impairing mucociliary clearance and increasing susceptibility to infection.

These virulence factors work together to enable Bordetella pertussis to colonize the respiratory tract, evade the host immune response, and cause the symptoms of whooping cough.

Allosteric regulation is a process that describes the way in which the binding of a molecule (known as a ligand) to an enzyme or protein at one site affects the ability of another molecule to bind to a different site on the same enzyme or protein. This interaction can either enhance (positive allosteric regulation) or inhibit (negative allosteric regulation) the activity of the enzyme or protein, depending on the nature of the ligand and its effect on the shape and/or conformation of the enzyme or protein.

In an allosteric regulatory system, the binding of the first molecule to the enzyme or protein causes a conformational change in the protein structure that alters the affinity of the second site for its ligand. This can result in changes in the activity of the enzyme or protein, allowing for fine-tuning of biochemical pathways and regulatory processes within cells.

Allosteric regulation is a fundamental mechanism in many biological systems, including metabolic pathways, signal transduction cascades, and gene expression networks. Understanding allosteric regulation can provide valuable insights into the mechanisms underlying various physiological and pathological processes, and can inform the development of novel therapeutic strategies for the treatment of disease.

Inositol phosphates are a family of molecules that consist of an inositol ring, which is a six-carbon heterocyclic compound, linked to one or more phosphate groups. These molecules play important roles as intracellular signaling intermediates and are involved in various cellular processes such as cell growth, differentiation, and metabolism.

Inositol hexakisphosphate (IP6), also known as phytic acid, is a form of inositol phosphate that is found in plant-based foods. IP6 has the ability to bind to minerals such as calcium, magnesium, and iron, which can reduce their bioavailability in the body.

Inositol phosphates have been implicated in several diseases, including cancer, diabetes, and neurodegenerative disorders. For example, altered levels of certain inositol phosphates have been observed in cancer cells, suggesting that they may play a role in tumor growth and progression. Additionally, mutations in enzymes involved in the metabolism of inositol phosphates have been associated with several genetic diseases.

Cholinergic fibers are nerve cell extensions (neurons) that release the neurotransmitter acetylcholine at their synapses, which are the junctions where they transmit signals to other neurons or effector cells such as muscles and glands. These fibers are a part of the cholinergic system, which plays crucial roles in various physiological processes including learning and memory, attention, arousal, sleep, and muscle contraction.

Cholinergic fibers can be found in both the central nervous system (CNS) and the peripheral nervous system (PNS). In the CNS, cholinergic neurons are primarily located in the basal forebrain and brainstem, and their projections innervate various regions of the cerebral cortex, hippocampus, thalamus, and other brain areas. In the PNS, cholinergic fibers are responsible for activating skeletal muscles through neuromuscular junctions, as well as regulating functions in smooth muscles, cardiac muscles, and glands via the autonomic nervous system.

Dysfunction of the cholinergic system has been implicated in several neurological disorders, such as Alzheimer's disease, Parkinson's disease, and myasthenia gravis.

"Competitive binding" is a term used in pharmacology and biochemistry to describe the behavior of two or more molecules (ligands) competing for the same binding site on a target protein or receptor. In this context, "binding" refers to the physical interaction between a ligand and its target.

When a ligand binds to a receptor, it can alter the receptor's function, either activating or inhibiting it. If multiple ligands compete for the same binding site, they will compete to bind to the receptor. The ability of each ligand to bind to the receptor is influenced by its affinity for the receptor, which is a measure of how strongly and specifically the ligand binds to the receptor.

In competitive binding, if one ligand is present in high concentrations, it can prevent other ligands with lower affinity from binding to the receptor. This is because the higher-affinity ligand will have a greater probability of occupying the binding site and blocking access to the other ligands. The competition between ligands can be described mathematically using equations such as the Langmuir isotherm, which describes the relationship between the concentration of ligand and the fraction of receptors that are occupied by the ligand.

Competitive binding is an important concept in drug development, as it can be used to predict how different drugs will interact with their targets and how they may affect each other's activity. By understanding the competitive binding properties of a drug, researchers can optimize its dosage and delivery to maximize its therapeutic effect while minimizing unwanted side effects.

Propylbenzilylcholine mustard is not a medical term, but it is a chemical compound that has been used in research and development. It's a type of muscarinic receptor agonist, which means it binds to and activates muscarinic acetylcholine receptors, a type of receptor found in the nervous system.

In a medical context, this compound may be used in research to study the functions of the muscarinic receptors or to develop new medications that target these receptors. However, it is not currently used as a medication in clinical practice.

It's important to note that Propylbenzilylcholine mustard is also known as a "receptor agonist" and has been used in research as a tool to stimulate muscarinic receptors. It's not a drug, but a compound used in laboratory settings for scientific studies.

The heart atria are the upper chambers of the heart that receive blood from the veins and deliver it to the lower chambers, or ventricles. There are two atria in the heart: the right atrium receives oxygen-poor blood from the body and pumps it into the right ventricle, which then sends it to the lungs to be oxygenated; and the left atrium receives oxygen-rich blood from the lungs and pumps it into the left ventricle, which then sends it out to the rest of the body. The atria contract before the ventricles during each heartbeat, helping to fill the ventricles with blood and prepare them for contraction.

G protein-coupled inwardly-rectifying potassium channels (GIRK channels) are a type of potassium channel that are activated by G proteins, which are molecules that help transmit signals within cells. These channels are characterized by their ability to allow potassium ions to flow into the cell more easily than they allow potassium ions to flow out of the cell, hence the term "inwardly-rectifying."

GIRK channels play a role in regulating various physiological processes, including neurotransmission, heart rate, and insulin secretion. They are activated by several different G proteins, including those that are activated by certain neurotransmitters and hormones. When these G proteins bind to the channel, they cause it to open, allowing potassium ions to flow into the cell. This can have various effects on the cell, depending on the type of cell and the specific signals being transmitted.

GIRK channels are composed of four subunits, each of which contains a pore through which potassium ions can pass. These subunits can be made up of different types of proteins, and the specific combination of subunits in a channel can affect its properties and regulation. Mutations in genes that encode GIRK channel subunits have been linked to various diseases, including certain forms of epilepsy and cardiac arrhythmias.

RGS (Regulator of G-protein Signaling) proteins are a group of regulatory molecules that interact with and modulate the activity of heterotrimeric G proteins, which are involved in various cellular signaling pathways. These proteins contain a conserved RGS domain, which functions as a GTPase-activating protein (GAP) for the alpha subunit of G proteins, thereby promoting the hydrolysis of GTP to GDP and terminating the signal transduction process. By regulating G protein signaling, RGS proteins play crucial roles in various physiological processes, including neurotransmission, cardiovascular function, immune response, and cell growth and differentiation. Dysregulation of RGS proteins has been implicated in several diseases, such as hypertension, cancer, and neurological disorders.

I could not find a medical definition for "Benzilates" as it is not a recognized term in medicine or pharmacology. It seems that you may have made a typographical error, and the correct term you are looking for might be "benzoylates." Benzoylates refer to salts or esters of benzoic acid, which have various uses including as preservatives and pharmaceutical ingredients.

If you meant something else by "Benzilates," please provide more context so I can give a more accurate response.

Arecoline is a parasympathomimetic alkaloid that is the primary active component found in the areca nut, which is chewed for its psychoactive effects in various parts of the world. It can cause stimulation of the nervous system and has been associated with several health risks, including oral cancer and cardiovascular disease.

The medical definition of Arecoline is:

A parasympathomimetic alkaloid found in the areca nut, which is chewed for its psychoactive effects. It stimulates the nervous system and has been associated with several health risks, including oral cancer and cardiovascular disease. The chemical formula for Arecoline is C7H9NO2.

Phthalimides are organic compounds that contain a phthalimide functional group. The phthalimide group consists of a pair of fused rings, a benzene ring and a five-membered ring containing two nitrogen atoms, with one of the nitrogen atoms being part of a carbonyl group.

Phthalimides are commonly used as intermediates in the synthesis of other organic compounds, including pharmaceuticals, agrochemicals, and dyes. They can also exhibit various biological activities, such as anti-inflammatory, antiviral, and anticancer properties. However, some phthalimides have been found to have toxic effects and may pose environmental and health concerns.

Calcium is an essential mineral that is vital for various physiological processes in the human body. The medical definition of calcium is as follows:

Calcium (Ca2+) is a crucial cation and the most abundant mineral in the human body, with approximately 99% of it found in bones and teeth. It plays a vital role in maintaining structural integrity, nerve impulse transmission, muscle contraction, hormonal secretion, blood coagulation, and enzyme activation.

Calcium homeostasis is tightly regulated through the interplay of several hormones, including parathyroid hormone (PTH), calcitonin, and vitamin D. Dietary calcium intake, absorption, and excretion are also critical factors in maintaining optimal calcium levels in the body.

Hypocalcemia refers to low serum calcium levels, while hypercalcemia indicates high serum calcium levels. Both conditions can have detrimental effects on various organ systems and require medical intervention to correct.

Sprague-Dawley rats are a strain of albino laboratory rats that are widely used in scientific research. They were first developed by researchers H.H. Sprague and R.C. Dawley in the early 20th century, and have since become one of the most commonly used rat strains in biomedical research due to their relatively large size, ease of handling, and consistent genetic background.

Sprague-Dawley rats are outbred, which means that they are genetically diverse and do not suffer from the same limitations as inbred strains, which can have reduced fertility and increased susceptibility to certain diseases. They are also characterized by their docile nature and low levels of aggression, making them easier to handle and study than some other rat strains.

These rats are used in a wide variety of research areas, including toxicology, pharmacology, nutrition, cancer, and behavioral studies. Because they are genetically diverse, Sprague-Dawley rats can be used to model a range of human diseases and conditions, making them an important tool in the development of new drugs and therapies.

Phospholipase C beta (PLCβ) is an enzyme that plays a crucial role in intracellular signaling transduction pathways. It is a subtype of Phospholipase C, which is responsible for cleaving phospholipids into secondary messengers, thereby mediating various cellular responses.

PLCβ is activated by G protein-coupled receptors (GPCRs) and can be found in various tissues throughout the body. Once activated, PLCβ hydrolyzes a specific phospholipid, PIP2 (Phosphatidylinositol 4,5-bisphosphate), into two secondary messengers: IP3 (Inositol 1,4,5-trisphosphate) and DAG (Diacylglycerol). These second messengers then trigger a series of downstream events, such as calcium mobilization and protein kinase C activation, which ultimately lead to changes in cell functions, including gene expression, cell growth, differentiation, and secretion.

There are four isoforms of PLCβ (PLCβ1, PLCβ2, PLCβ3, and PLCβ4) that differ in their tissue distribution, regulation, and substrate specificity. Mutations or dysregulation of PLCβ have been implicated in several diseases, including cancer, cardiovascular disease, and neurological disorders.

Quinuclidines are a class of organic compounds that contain a unique cage-like structure consisting of a tetrahydrofuran ring fused to a piperidine ring. The name "quinuclidine" is derived from the Latin word "quinque," meaning five, and "clidis," meaning key or bar, which refers to the five-membered ring system that forms the core of these compounds.

Quinuclidines have a variety of biological activities and are used in pharmaceuticals as well as agrochemicals. Some quinuclidine derivatives have been found to exhibit anti-inflammatory, antiviral, and anticancer properties. They can also act as inhibitors of various enzymes and receptors, making them useful tools for studying biological systems and developing new drugs.

It is worth noting that quinuclidines are not typically used in medical diagnosis or treatment, but rather serve as building blocks for the development of new pharmaceutical compounds.

An allosteric site is a distinct and separate binding site on a protein (usually an enzyme) other than the active site where the substrate binds. The binding of a molecule (known as an allosteric modulator or effector) to this site can cause a conformational change in the protein's structure, which in turn affects its activity, either by enhancing (allosteric activation) or inhibiting (allosteric inhibition) its function. This allosteric regulation allows for complex control mechanisms in biological systems and is crucial for many cellular processes.

Methacholine compounds are medications that are used as a diagnostic tool to help identify and confirm the presence of airway hyperresponsiveness in patients with respiratory symptoms such as cough, wheeze, or shortness of breath. These compounds act as bronchoconstrictors, causing narrowing of the airways in individuals who have heightened sensitivity and reactivity of their airways, such as those with asthma.

Methacholine is a synthetic derivative of acetylcholine, a neurotransmitter that mediates nerve impulse transmission in the body. When inhaled, methacholine binds to muscarinic receptors on the smooth muscle surrounding the airways, leading to their contraction and narrowing. The degree of bronchoconstriction is then measured to assess the patient's airway responsiveness.

It is important to note that methacholine compounds are not used as therapeutic agents but rather as diagnostic tools in a controlled medical setting under the supervision of healthcare professionals.

Quinuclidinyl benzilate is a synthetic chemical compound that acts as a potent anticholinergic drug. Its chemical formula is C18H26N2O2. It is an odorless, white crystalline powder that is slightly soluble in water and more soluble in organic solvents.

Quinuclidinyl benzilate is a deliriant drug, which means it can cause delirium, confusion, hallucinations, and other altered mental states. It works by blocking the action of acetylcholine, a neurotransmitter in the brain that is involved in memory, attention, and perception.

This compound has been used in research as a tool to study the nervous system and has also been explored for its potential use as a chemical weapon. It is classified as a Schedule II controlled substance in the United States due to its high potential for abuse and the risk of severe psychological harm.

Electric stimulation, also known as electrical nerve stimulation or neuromuscular electrical stimulation, is a therapeutic treatment that uses low-voltage electrical currents to stimulate nerves and muscles. It is often used to help manage pain, promote healing, and improve muscle strength and mobility. The electrical impulses can be delivered through electrodes placed on the skin or directly implanted into the body.

In a medical context, electric stimulation may be used for various purposes such as:

1. Pain management: Electric stimulation can help to block pain signals from reaching the brain and promote the release of endorphins, which are natural painkillers produced by the body.
2. Muscle rehabilitation: Electric stimulation can help to strengthen muscles that have become weak due to injury, illness, or surgery. It can also help to prevent muscle atrophy and improve range of motion.
3. Wound healing: Electric stimulation can promote tissue growth and help to speed up the healing process in wounds, ulcers, and other types of injuries.
4. Urinary incontinence: Electric stimulation can be used to strengthen the muscles that control urination and reduce symptoms of urinary incontinence.
5. Migraine prevention: Electric stimulation can be used as a preventive treatment for migraines by applying electrical impulses to specific nerves in the head and neck.

It is important to note that electric stimulation should only be administered under the guidance of a qualified healthcare professional, as improper use can cause harm or discomfort.

Tritium is not a medical term, but it is a term used in the field of nuclear physics and chemistry. Tritium (symbol: T or 3H) is a radioactive isotope of hydrogen with two neutrons and one proton in its nucleus. It is also known as heavy hydrogen or superheavy hydrogen.

Tritium has a half-life of about 12.3 years, which means that it decays by emitting a low-energy beta particle (an electron) to become helium-3. Due to its radioactive nature and relatively short half-life, tritium is used in various applications, including nuclear weapons, fusion reactors, luminous paints, and medical research.

In the context of medicine, tritium may be used as a radioactive tracer in some scientific studies or medical research, but it is not a term commonly used to describe a medical condition or treatment.

Cholinergic receptors are a type of receptor in the body that are activated by the neurotransmitter acetylcholine. Acetylcholine is a chemical that nerve cells use to communicate with each other and with muscles. There are two main types of cholinergic receptors: muscarinic and nicotinic.

Muscarinic receptors are found in the heart, smooth muscle, glands, and the central nervous system. They are activated by muscarine, a type of alkaloid found in certain mushrooms. When muscarinic receptors are activated, they can cause changes in heart rate, blood pressure, and other bodily functions.

Nicotinic receptors are found in the nervous system and at the junction between nerves and muscles (the neuromuscular junction). They are activated by nicotine, a type of alkaloid found in tobacco plants. When nicotinic receptors are activated, they can cause the release of neurotransmitters and the contraction of muscles.

Cholinergic receptors play an important role in many physiological processes, including learning, memory, and movement. They are also targets for drugs used to treat a variety of medical conditions, such as Alzheimer's disease, Parkinson's disease, and myasthenia gravis (a disorder that causes muscle weakness).

The Parasympathetic Nervous System (PNS) is the part of the autonomic nervous system that primarily controls vegetative functions during rest, relaxation, and digestion. It is responsible for the body's "rest and digest" activities including decreasing heart rate, lowering blood pressure, increasing digestive activity, and stimulating sexual arousal. The PNS utilizes acetylcholine as its primary neurotransmitter and acts in opposition to the Sympathetic Nervous System (SNS), which is responsible for the "fight or flight" response.

Isoindoles are not typically considered in the context of medical definitions, as they are organic compounds that do not have direct relevance to medical terminology or human disease. However, isoindole is a heterocyclic compound that contains two nitrogen atoms in its structure and can be found in some naturally occurring substances and synthetic drugs.

Isoindoles are aromatic compounds, which means they have a stable ring structure with delocalized electrons. They can form the core structure of various bioactive molecules, including alkaloids, which are nitrogen-containing compounds that occur naturally in plants and animals and can have various pharmacological activities.

Some isoindole derivatives have been synthesized and studied for their potential medicinal properties, such as anti-inflammatory, antiviral, and anticancer activities. However, these compounds are still in the early stages of research and development and have not yet been approved for medical use.

Therefore, while isoindoles themselves do not have a specific medical definition, they can be relevant to the study of medicinal chemistry and drug discovery.

"Wistar rats" are a strain of albino rats that are widely used in laboratory research. They were developed at the Wistar Institute in Philadelphia, USA, and were first introduced in 1906. Wistar rats are outbred, which means that they are genetically diverse and do not have a fixed set of genetic characteristics like inbred strains.

Wistar rats are commonly used as animal models in biomedical research because of their size, ease of handling, and relatively low cost. They are used in a wide range of research areas, including toxicology, pharmacology, nutrition, cancer, cardiovascular disease, and behavioral studies. Wistar rats are also used in safety testing of drugs, medical devices, and other products.

Wistar rats are typically larger than many other rat strains, with males weighing between 500-700 grams and females weighing between 250-350 grams. They have a lifespan of approximately 2-3 years. Wistar rats are also known for their docile and friendly nature, making them easy to handle and work with in the laboratory setting.

Patch-clamp techniques are a group of electrophysiological methods used to study ion channels and other electrical properties of cells. These techniques were developed by Erwin Neher and Bert Sakmann, who were awarded the Nobel Prize in Physiology or Medicine in 1991 for their work. The basic principle of patch-clamp techniques involves creating a high resistance seal between a glass micropipette and the cell membrane, allowing for the measurement of current flowing through individual ion channels or groups of channels.

There are several different configurations of patch-clamp techniques, including:

1. Cell-attached configuration: In this configuration, the micropipette is attached to the outer surface of the cell membrane, and the current flowing across a single ion channel can be measured. This configuration allows for the study of the properties of individual channels in their native environment.
2. Whole-cell configuration: Here, the micropipette breaks through the cell membrane, creating a low resistance electrical connection between the pipette and the inside of the cell. This configuration allows for the measurement of the total current flowing across all ion channels in the cell membrane.
3. Inside-out configuration: In this configuration, the micropipette is pulled away from the cell after establishing a seal, resulting in the exposure of the inner surface of the cell membrane to the solution in the pipette. This configuration allows for the study of the properties of ion channels in isolation from other cellular components.
4. Outside-out configuration: Here, the micropipette is pulled away from the cell after establishing a seal, resulting in the exposure of the outer surface of the cell membrane to the solution in the pipette. This configuration allows for the study of the properties of ion channels in their native environment, but with the ability to control the composition of the extracellular solution.

Patch-clamp techniques have been instrumental in advancing our understanding of ion channel function and have contributed to numerous breakthroughs in neuroscience, pharmacology, and physiology.

Bethanechol compounds are a type of cholinergic agent used in medical treatment. They are parasympathomimetic drugs, which means they mimic the actions of the neurotransmitter acetylcholine at muscarinic receptors. Specifically, bethanechol compounds stimulate the muscarinic receptors in the smooth muscle of the bladder and gastrointestinal tract, increasing tone and promoting contractions.

Bethanechol is primarily used to treat urinary retention and associated symptoms, such as those that can occur after certain types of surgery or with conditions like spinal cord injury or multiple sclerosis. It works by helping the bladder muscle contract, which can promote urination.

It's important to note that bethanechol should be used with caution, as it can have various side effects, including sweating, increased salivation, flushed skin, and gastrointestinal symptoms like nausea, vomiting, or diarrhea. It may also interact with other medications, so it's crucial to discuss any potential risks with a healthcare provider before starting this treatment.

Muscle relaxation, in a medical context, refers to the process of reducing tension and promoting relaxation in the skeletal muscles. This can be achieved through various techniques, including progressive muscle relaxation (PMR), where individuals consciously tense and then release specific muscle groups in a systematic manner.

PMR has been shown to help reduce anxiety, stress, and muscle tightness, and improve overall well-being. It is often used as a complementary therapy in conjunction with other treatments for conditions such as chronic pain, headaches, and insomnia.

Additionally, muscle relaxation can also be facilitated through pharmacological interventions, such as the use of muscle relaxant medications. These drugs work by inhibiting the transmission of signals between nerves and muscles, leading to a reduction in muscle tone and spasticity. They are commonly used to treat conditions such as multiple sclerosis, cerebral palsy, and spinal cord injuries.

In the context of medicine and pharmacology, "kinetics" refers to the study of how a drug moves throughout the body, including its absorption, distribution, metabolism, and excretion (often abbreviated as ADME). This field is called "pharmacokinetics."

1. Absorption: This is the process of a drug moving from its site of administration into the bloodstream. Factors such as the route of administration (e.g., oral, intravenous, etc.), formulation, and individual physiological differences can affect absorption.

2. Distribution: Once a drug is in the bloodstream, it gets distributed throughout the body to various tissues and organs. This process is influenced by factors like blood flow, protein binding, and lipid solubility of the drug.

3. Metabolism: Drugs are often chemically modified in the body, typically in the liver, through processes known as metabolism. These changes can lead to the formation of active or inactive metabolites, which may then be further distributed, excreted, or undergo additional metabolic transformations.

4. Excretion: This is the process by which drugs and their metabolites are eliminated from the body, primarily through the kidneys (urine) and the liver (bile).

Understanding the kinetics of a drug is crucial for determining its optimal dosing regimen, potential interactions with other medications or foods, and any necessary adjustments for special populations like pediatric or geriatric patients, or those with impaired renal or hepatic function.

Transfection is a term used in molecular biology that refers to the process of deliberately introducing foreign genetic material (DNA, RNA or artificial gene constructs) into cells. This is typically done using chemical or physical methods, such as lipofection or electroporation. Transfection is widely used in research and medical settings for various purposes, including studying gene function, producing proteins, developing gene therapies, and creating genetically modified organisms. It's important to note that transfection is different from transduction, which is the process of introducing genetic material into cells using viruses as vectors.

Isoproterenol is a medication that belongs to a class of drugs called beta-adrenergic agonists. Medically, it is defined as a synthetic catecholamine with both alpha and beta adrenergic receptor stimulating properties. It is primarily used as a bronchodilator to treat conditions such as asthma and chronic obstructive pulmonary disease (COPD) by relaxing the smooth muscles in the airways, thereby improving breathing.

Isoproterenol can also be used in the treatment of bradycardia (abnormally slow heart rate), cardiac arrest, and heart blocks by increasing the heart rate and contractility. However, due to its non-selective beta-agonist activity, it may cause various side effects such as tremors, palpitations, and increased blood pressure. Its use is now limited due to the availability of more selective and safer medications.

Signal transduction is the process by which a cell converts an extracellular signal, such as a hormone or neurotransmitter, into an intracellular response. This involves a series of molecular events that transmit the signal from the cell surface to the interior of the cell, ultimately resulting in changes in gene expression, protein activity, or metabolism.

The process typically begins with the binding of the extracellular signal to a receptor located on the cell membrane. This binding event activates the receptor, which then triggers a cascade of intracellular signaling molecules, such as second messengers, protein kinases, and ion channels. These molecules amplify and propagate the signal, ultimately leading to the activation or inhibition of specific cellular responses.

Signal transduction pathways are highly regulated and can be modulated by various factors, including other signaling molecules, post-translational modifications, and feedback mechanisms. Dysregulation of these pathways has been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.

Potassium channels are membrane proteins that play a crucial role in regulating the electrical excitability of cells, including cardiac, neuronal, and muscle cells. These channels facilitate the selective passage of potassium ions (K+) across the cell membrane, maintaining the resting membrane potential and shaping action potentials. They are composed of four or six subunits that assemble to form a central pore through which potassium ions move down their electrochemical gradient. Potassium channels can be modulated by various factors such as voltage, ligands, mechanical stimuli, or temperature, allowing cells to fine-tune their electrical properties and respond to different physiological demands. Dysfunction of potassium channels has been implicated in several diseases, including cardiac arrhythmias, epilepsy, and neurodegenerative disorders.

I'm sorry for any confusion, but "Pyridines" is not a medical term. It is a chemical term that refers to a class of organic compounds with the chemical structure of a six-membered ring containing one nitrogen atom and five carbon atoms (heterocyclic aromatic compound).

In a biological or medical context, pyridine derivatives can be found in various natural and synthetic substances. For example, some medications contain pyridine rings as part of their chemical structure. However, "Pyridines" itself is not a medical term or condition.

Inositol 1,4,5-trisphosphate (IP3) is a intracellular signaling molecule that plays a crucial role in the release of calcium ions from the endoplasmic reticulum into the cytoplasm. It is a second messenger, which means it relays signals received by a cell's surface receptors to various effector proteins within the cell. IP3 is produced through the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) by activated phospholipase C (PLC) enzymes in response to extracellular signals such as hormones and neurotransmitters. The binding of IP3 to its receptor on the endoplasmic reticulum triggers the release of calcium ions, which then activates various cellular processes like gene expression, metabolism, and muscle contraction.

I'm sorry for any confusion, but "Dexetimide" doesn't seem to be a recognized medication or substance in modern medical terminology, at least not in English. It's possible that it might be an obscure or outdated term, or perhaps it's used in a different language or context.

If you have more context or information about where you encountered this term, I might be able to provide a more accurate response. However, without further information, I can't provide a reliable medical definition for "Dexetimide".

Cyclic adenosine monophosphate (cAMP) is a key secondary messenger in many biological processes, including the regulation of metabolism, gene expression, and cellular excitability. It is synthesized from adenosine triphosphate (ATP) by the enzyme adenylyl cyclase and is degraded by the enzyme phosphodiesterase.

In the body, cAMP plays a crucial role in mediating the effects of hormones and neurotransmitters on target cells. For example, when a hormone binds to its receptor on the surface of a cell, it can activate a G protein, which in turn activates adenylyl cyclase to produce cAMP. The increased levels of cAMP then activate various effector proteins, such as protein kinases, which go on to regulate various cellular processes.

Overall, the regulation of cAMP levels is critical for maintaining proper cellular function and homeostasis, and abnormalities in cAMP signaling have been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.

Presynaptic receptors are a type of neuroreceptor located on the presynaptic membrane of a neuron, which is the side that releases neurotransmitters. These receptors can be activated by neurotransmitters or other signaling molecules released from the postsynaptic neuron or from other nearby cells.

When activated, presynaptic receptors can modulate the release of neurotransmitters from the presynaptic neuron. They can have either an inhibitory or excitatory effect on neurotransmitter release, depending on the type of receptor and the signaling molecule that binds to it.

For example, activation of certain presynaptic receptors can decrease the amount of calcium that enters the presynaptic terminal, which in turn reduces the amount of neurotransmitter released into the synapse. Other presynaptic receptors, when activated, can increase the release of neurotransmitters.

Presynaptic receptors play an important role in regulating neuronal communication and are involved in various physiological processes, including learning, memory, and pain perception. They are also targeted by certain drugs used to treat neurological and psychiatric disorders.

Membrane potential is the electrical potential difference across a cell membrane, typically for excitable cells such as nerve and muscle cells. It is the difference in electric charge between the inside and outside of a cell, created by the selective permeability of the cell membrane to different ions. The resting membrane potential of a typical animal cell is around -70 mV, with the interior being negative relative to the exterior. This potential is generated and maintained by the active transport of ions across the membrane, primarily through the action of the sodium-potassium pump. Membrane potentials play a crucial role in many physiological processes, including the transmission of nerve impulses and the contraction of muscle cells.

Receptor cross-talk, also known as receptor crosstalk or cross-communication, refers to the phenomenon where two or more receptors in a cell interact with each other and modulate their signals in a coordinated manner. This interaction can occur at various levels, such as sharing downstream signaling pathways, physically interacting with each other, or influencing each other's expression or activity.

In the context of G protein-coupled receptors (GPCRs), which are a large family of membrane receptors that play crucial roles in various physiological processes, cross-talk can occur between different GPCRs or between GPCRs and other types of receptors. For example, one GPCR may activate a signaling pathway that inhibits the activity of another GPCR, leading to complex regulatory mechanisms that allow cells to fine-tune their responses to various stimuli.

Receptor cross-talk can have important implications for drug development and therapy, as it can affect the efficacy and safety of drugs that target specific receptors. Understanding the mechanisms of receptor cross-talk can help researchers design more effective and targeted therapies for a wide range of diseases.

Physostigmine is a medication that belongs to a class of drugs called cholinesterase inhibitors. It works by blocking the breakdown of a neurotransmitter called acetylcholine, which is important for communication between nerves and muscles. This results in an increase in acetylcholine levels in the body, improving nerve impulse transmission and helping to restore normal muscle function.

Physostigmine is used in the treatment of certain medical conditions that are caused by a deficiency of acetylcholine, such as myasthenia gravis, which is a neuromuscular disorder characterized by weakness and fatigue of the muscles. It may also be used to reverse the effects of certain medications that block the action of acetylcholine, such as anticholinergics, which are sometimes used in anesthesia or to treat conditions like Parkinson's disease.

It is important to note that physostigmine should only be used under the close supervision of a healthcare provider, as it can have serious side effects if not used properly.

Parasympathetic ganglia are collections of neurons located outside the central nervous system (CNS) that serve as relay stations for parasympathetic nerve impulses. The parasympathetic nervous system is one of the two subdivisions of the autonomic nervous system, which controls involuntary physiological responses.

The parasympathetic ganglia receive preganglionic fibers from the brainstem and sacral regions of the spinal cord. After synapsing in these ganglia, postganglionic fibers innervate target organs such as the heart, glands, and smooth muscles. The primary function of the parasympathetic nervous system is to promote rest, digestion, and energy conservation.

Parasympathetic ganglia are typically located close to or within the target organs they innervate. Examples include:

1. Ciliary ganglion: Innervates the ciliary muscle and iris sphincter in the eye, controlling accommodation and pupil constriction.
2. Pterygopalatine (sphenopalatine) ganglion: Supplies the lacrimal gland, mucous membranes of the nasal cavity, and palate, regulating tear production and nasal secretions.
3. Otic ganglion: Innervates the parotid gland, controlling salivary secretion.
4. Submandibular ganglion: Supplies the submandibular and sublingual salivary glands, regulating salivation.
5. Sacral parasympathetic ganglia: Located in the sacrum, they innervate the distal colon, rectum, and genitourinary organs, controlling defecation, urination, and sexual arousal.

These parasympathetic ganglia play crucial roles in maintaining homeostasis by regulating various bodily functions during rest and relaxation.

Adenylate cyclase is an enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP). It plays a crucial role in various cellular processes, including signal transduction and metabolism. Adenylate cyclase is activated by hormones and neurotransmitters that bind to G-protein-coupled receptors on the cell membrane, leading to the production of cAMP, which then acts as a second messenger to regulate various intracellular responses. There are several isoforms of adenylate cyclase, each with distinct regulatory properties and subcellular localization.

The myocardium is the middle layer of the heart wall, composed of specialized cardiac muscle cells that are responsible for pumping blood throughout the body. It forms the thickest part of the heart wall and is divided into two sections: the left ventricle, which pumps oxygenated blood to the rest of the body, and the right ventricle, which pumps deoxygenated blood to the lungs.

The myocardium contains several types of cells, including cardiac muscle fibers, connective tissue, nerves, and blood vessels. The muscle fibers are arranged in a highly organized pattern that allows them to contract in a coordinated manner, generating the force necessary to pump blood through the heart and circulatory system.

Damage to the myocardium can occur due to various factors such as ischemia (reduced blood flow), infection, inflammation, or genetic disorders. This damage can lead to several cardiac conditions, including heart failure, arrhythmias, and cardiomyopathy.

"Cells, cultured" is a medical term that refers to cells that have been removed from an organism and grown in controlled laboratory conditions outside of the body. This process is called cell culture and it allows scientists to study cells in a more controlled and accessible environment than they would have inside the body. Cultured cells can be derived from a variety of sources, including tissues, organs, or fluids from humans, animals, or cell lines that have been previously established in the laboratory.

Cell culture involves several steps, including isolation of the cells from the tissue, purification and characterization of the cells, and maintenance of the cells in appropriate growth conditions. The cells are typically grown in specialized media that contain nutrients, growth factors, and other components necessary for their survival and proliferation. Cultured cells can be used for a variety of purposes, including basic research, drug development and testing, and production of biological products such as vaccines and gene therapies.

It is important to note that cultured cells may behave differently than they do in the body, and results obtained from cell culture studies may not always translate directly to human physiology or disease. Therefore, it is essential to validate findings from cell culture experiments using additional models and ultimately in clinical trials involving human subjects.

In medical terms, the heart is a muscular organ located in the thoracic cavity that functions as a pump to circulate blood throughout the body. It's responsible for delivering oxygen and nutrients to the tissues and removing carbon dioxide and other wastes. The human heart is divided into four chambers: two atria on the top and two ventricles on the bottom. The right side of the heart receives deoxygenated blood from the body and pumps it to the lungs, while the left side receives oxygenated blood from the lungs and pumps it out to the rest of the body. The heart's rhythmic contractions and relaxations are regulated by a complex electrical conduction system.

A cell membrane, also known as the plasma membrane, is a thin semi-permeable phospholipid bilayer that surrounds all cells in animals, plants, and microorganisms. It functions as a barrier to control the movement of substances in and out of the cell, allowing necessary molecules such as nutrients, oxygen, and signaling molecules to enter while keeping out harmful substances and waste products. The cell membrane is composed mainly of phospholipids, which have hydrophilic (water-loving) heads and hydrophobic (water-fearing) tails. This unique structure allows the membrane to be flexible and fluid, yet selectively permeable. Additionally, various proteins are embedded in the membrane that serve as channels, pumps, receptors, and enzymes, contributing to the cell's overall functionality and communication with its environment.

Neurons, also known as nerve cells or neurocytes, are specialized cells that constitute the basic unit of the nervous system. They are responsible for receiving, processing, and transmitting information and signals within the body. Neurons have three main parts: the dendrites, the cell body (soma), and the axon. The dendrites receive signals from other neurons or sensory receptors, while the axon transmits these signals to other neurons, muscles, or glands. The junction between two neurons is called a synapse, where neurotransmitters are released to transmit the signal across the gap (synaptic cleft) to the next neuron. Neurons vary in size, shape, and structure depending on their function and location within the nervous system.

Cholinergic antagonists, also known as anticholinergics or parasympatholytics, are a class of drugs that block the action of the neurotransmitter acetylcholine in the nervous system. They achieve this by binding to and blocking the activation of muscarinic acetylcholine receptors, which are found in various organs throughout the body, including the eyes, lungs, heart, gastrointestinal tract, and urinary bladder.

The blockade of these receptors results in a range of effects depending on the specific organ system involved. For example, cholinergic antagonists can cause mydriasis (dilation of the pupils), cycloplegia (paralysis of the ciliary muscle of the eye), tachycardia (rapid heart rate), reduced gastrointestinal motility and secretion, urinary retention, and respiratory tract smooth muscle relaxation.

Cholinergic antagonists are used in a variety of clinical settings, including the treatment of conditions such as Parkinson's disease, chronic obstructive pulmonary disease (COPD), asthma, gastrointestinal disorders, and urinary incontinence. Some common examples of cholinergic antagonists include atropine, scopolamine, ipratropium, and oxybutynin.

It's important to note that cholinergic antagonists can have significant side effects, particularly when used in high doses or in combination with other medications that affect the nervous system. These side effects can include confusion, memory impairment, hallucinations, delirium, and blurred vision. Therefore, it's essential to use these drugs under the close supervision of a healthcare provider and to follow their instructions carefully.

Cholinesterase inhibitors are a class of drugs that work by blocking the action of cholinesterase, an enzyme that breaks down the neurotransmitter acetylcholine in the body. By inhibiting this enzyme, the levels of acetylcholine in the brain increase, which can help to improve symptoms of cognitive decline and memory loss associated with conditions such as Alzheimer's disease and other forms of dementia.

Cholinesterase inhibitors are also used to treat other medical conditions, including myasthenia gravis, a neuromuscular disorder that causes muscle weakness, and glaucoma, a condition that affects the optic nerve and can lead to vision loss. Some examples of cholinesterase inhibitors include donepezil (Aricept), galantamine (Razadyne), and rivastigmine (Exelon).

It's important to note that while cholinesterase inhibitors can help to improve symptoms in some people with dementia, they do not cure the underlying condition or stop its progression. Side effects of these drugs may include nausea, vomiting, diarrhea, and increased salivation. In rare cases, they may also cause seizures, fainting, or cardiac arrhythmias.

Atropine derivatives are a class of drugs that are chemically related to atropine, an alkaloid found in the nightshade family of plants. These drugs have anticholinergic properties, which means they block the action of the neurotransmitter acetylcholine in the body.

Atropine derivatives can be used for a variety of medical purposes, including:

1. Treating motion sickness and vertigo
2. Dilating the pupils during eye examinations
3. Reducing saliva production during surgical procedures
4. Treating certain types of poisoning, such as organophosphate or nerve gas poisoning
5. Managing symptoms of some neurological disorders, such as Parkinson's disease and myasthenia gravis

Some examples of atropine derivatives include hyoscyamine, scopolamine, and ipratropium. These drugs can have side effects, including dry mouth, blurred vision, constipation, difficulty urinating, and rapid heartbeat. They should be used with caution and under the supervision of a healthcare provider.

The urinary bladder is a muscular, hollow organ in the pelvis that stores urine before it is released from the body. It expands as it fills with urine and contracts when emptying. The typical adult bladder can hold between 400 to 600 milliliters of urine for about 2-5 hours before the urge to urinate occurs. The wall of the bladder contains several layers, including a mucous membrane, a layer of smooth muscle (detrusor muscle), and an outer fibrous adventitia. The muscles of the bladder neck and urethra remain contracted to prevent leakage of urine during filling, and they relax during voiding to allow the urine to flow out through the urethra.

Protein Kinase C (PKC) is a family of serine-threonine kinases that play crucial roles in various cellular signaling pathways. These enzymes are activated by second messengers such as diacylglycerol (DAG) and calcium ions (Ca2+), which result from the activation of cell surface receptors like G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs).

Once activated, PKC proteins phosphorylate downstream target proteins, thereby modulating their activities. This regulation is involved in numerous cellular processes, including cell growth, differentiation, apoptosis, and membrane trafficking. There are at least 10 isoforms of PKC, classified into three subfamilies based on their second messenger requirements and structural features: conventional (cPKC; α, βI, βII, and γ), novel (nPKC; δ, ε, η, and θ), and atypical (aPKC; ζ and ι/λ). Dysregulation of PKC signaling has been implicated in several diseases, such as cancer, diabetes, and neurological disorders.

A drug interaction is the effect of combining two or more drugs, or a drug and another substance (such as food or alcohol), which can alter the effectiveness or side effects of one or both of the substances. These interactions can be categorized as follows:

1. Pharmacodynamic interactions: These occur when two or more drugs act on the same target organ or receptor, leading to an additive, synergistic, or antagonistic effect. For example, taking a sedative and an antihistamine together can result in increased drowsiness due to their combined depressant effects on the central nervous system.
2. Pharmacokinetic interactions: These occur when one drug affects the absorption, distribution, metabolism, or excretion of another drug. For example, taking certain antibiotics with grapefruit juice can increase the concentration of the antibiotic in the bloodstream, leading to potential toxicity.
3. Food-drug interactions: Some drugs may interact with specific foods, affecting their absorption, metabolism, or excretion. An example is the interaction between warfarin (a blood thinner) and green leafy vegetables, which can increase the risk of bleeding due to enhanced vitamin K absorption from the vegetables.
4. Drug-herb interactions: Some herbal supplements may interact with medications, leading to altered drug levels or increased side effects. For instance, St. John's Wort can decrease the effectiveness of certain antidepressants and oral contraceptives by inducing their metabolism.
5. Drug-alcohol interactions: Alcohol can interact with various medications, causing additive sedative effects, impaired judgment, or increased risk of liver damage. For example, combining alcohol with benzodiazepines or opioids can lead to dangerous levels of sedation and respiratory depression.

It is essential for healthcare providers and patients to be aware of potential drug interactions to minimize adverse effects and optimize treatment outcomes.

Inwardly rectifying potassium channels (Kir) are a type of potassium channel that allow for the selective passage of potassium ions (K+) across cell membranes. The term "inwardly rectifying" refers to their unique property of allowing potassium ions to flow more easily into the cell (inward current) than out of the cell (outward current). This characteristic is due to the voltage-dependent blockage of these channels by intracellular magnesium and polyamines at depolarized potentials.

These channels play crucial roles in various physiological processes, including:

1. Resting membrane potential maintenance: Kir channels help establish and maintain the negative resting membrane potential in cells by facilitating potassium efflux when the membrane potential is near the potassium equilibrium potential (Ek).
2. Action potential repolarization: In excitable cells like neurons and muscle fibers, Kir channels contribute to the rapid repolarization phase of action potentials, allowing for proper electrical signaling.
3. Cell volume regulation: Kir channels are involved in regulating cell volume by mediating potassium influx during osmotic stress or changes in intracellular ion concentrations.
4. Insulin secretion: In pancreatic β-cells, Kir channels control the membrane potential and calcium signaling necessary for insulin release.
5. Renal function: Kir channels are essential for maintaining electrolyte balance and controlling renal tubular transport in the kidneys.

There are several subfamilies of inwardly rectifying potassium channels (Kir1-7), each with distinct biophysical properties, tissue distributions, and functions. Mutations in genes encoding these channels can lead to various human diseases, including cardiac arrhythmias, epilepsy, and Bartter syndrome.

Alcuronium is a muscle relaxant that has been used in anesthesia to provide skeletal muscle relaxation during surgery. It works by blocking the transmission of nerve impulses at the neuromuscular junction, which leads to paralysis of the muscles. Alcuronium is no longer commonly used in clinical practice due to the development of newer and safer muscle relaxants.

The duodenum is the first part of the small intestine, immediately following the stomach. It is a C-shaped structure that is about 10-12 inches long and is responsible for continuing the digestion process that begins in the stomach. The duodenum receives partially digested food from the stomach through the pyloric valve and mixes it with digestive enzymes and bile produced by the pancreas and liver, respectively. These enzymes help break down proteins, fats, and carbohydrates into smaller molecules, allowing for efficient absorption in the remaining sections of the small intestine.

Hexamethonium compounds are a type of ganglionic blocker, which are medications that block the transmission of nerve impulses at the ganglia ( clusters of nerve cells) in the autonomic nervous system. These compounds contain hexamethonium as the active ingredient, which is a compound with the chemical formula C16H32N2O4.

Hexamethonium works by blocking the nicotinic acetylcholine receptors at the ganglia, which prevents the release of neurotransmitters and ultimately inhibits the transmission of nerve impulses. This can have various effects on the body, depending on which part of the autonomic nervous system is affected.

Hexamethonium compounds were once used to treat hypertension (high blood pressure), but they are rarely used today due to their numerous side effects and the availability of safer and more effective medications. Some of the side effects associated with hexamethonium include dry mouth, blurred vision, constipation, difficulty urinating, and dizziness upon standing.

A cell line is a culture of cells that are grown in a laboratory for use in research. These cells are usually taken from a single cell or group of cells, and they are able to divide and grow continuously in the lab. Cell lines can come from many different sources, including animals, plants, and humans. They are often used in scientific research to study cellular processes, disease mechanisms, and to test new drugs or treatments. Some common types of human cell lines include HeLa cells (which come from a cancer patient named Henrietta Lacks), HEK293 cells (which come from embryonic kidney cells), and HUVEC cells (which come from umbilical vein endothelial cells). It is important to note that cell lines are not the same as primary cells, which are cells that are taken directly from a living organism and have not been grown in the lab.

A ligand, in the context of biochemistry and medicine, is a molecule that binds to a specific site on a protein or a larger biomolecule, such as an enzyme or a receptor. This binding interaction can modify the function or activity of the target protein, either activating it or inhibiting it. Ligands can be small molecules, like hormones or neurotransmitters, or larger structures, like antibodies. The study of ligand-protein interactions is crucial for understanding cellular processes and developing drugs, as many therapeutic compounds function by binding to specific targets within the body.

G-protein-coupled receptors (GPCRs) are a family of membrane receptors that play an essential role in cellular signaling and communication. These receptors possess seven transmembrane domains, forming a structure that spans the lipid bilayer of the cell membrane. They are called "G-protein-coupled" because they interact with heterotrimeric G proteins upon activation, which in turn modulate various downstream signaling pathways.

When an extracellular ligand binds to a GPCR, it causes a conformational change in the receptor's structure, leading to the exchange of guanosine diphosphate (GDP) for guanosine triphosphate (GTP) on the associated G protein's α subunit. This exchange triggers the dissociation of the G protein into its α and βγ subunits, which then interact with various effector proteins to elicit cellular responses.

There are four main families of GPCRs, classified based on their sequence similarities and downstream signaling pathways:

1. Gq-coupled receptors: These receptors activate phospholipase C (PLC), which leads to the production of inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 induces calcium release from intracellular stores, while DAG activates protein kinase C (PKC).
2. Gs-coupled receptors: These receptors activate adenylyl cyclase, which increases the production of cyclic adenosine monophosphate (cAMP) and subsequently activates protein kinase A (PKA).
3. Gi/o-coupled receptors: These receptors inhibit adenylyl cyclase, reducing cAMP levels and modulating PKA activity. Additionally, they can activate ion channels or regulate other signaling pathways through the βγ subunits.
4. G12/13-coupled receptors: These receptors primarily activate RhoGEFs, which in turn activate RhoA and modulate cytoskeletal organization and cellular motility.

GPCRs are involved in various physiological processes, including neurotransmission, hormone signaling, immune response, and sensory perception. Dysregulation of GPCR function has been implicated in numerous diseases, making them attractive targets for drug development.

Hydrolysis is a chemical process, not a medical one. However, it is relevant to medicine and biology.

Hydrolysis is the breakdown of a chemical compound due to its reaction with water, often resulting in the formation of two or more simpler compounds. In the context of physiology and medicine, hydrolysis is a crucial process in various biological reactions, such as the digestion of food molecules like proteins, carbohydrates, and fats. Enzymes called hydrolases catalyze these hydrolysis reactions to speed up the breakdown process in the body.

Glycopyrrolate is an anticholinergic medication that works by blocking the action of acetylcholine, a chemical messenger in the body. It reduces the secretions of certain organs and is used to treat various conditions such as peptic ulcers, reducing saliva production during surgical procedures, preventing motion sickness, and managing some symptoms of Parkinson's disease.

In medical terms, glycopyrrolate is a competitive antagonist of muscarinic acetylcholine receptors. It has a particular affinity for the M1, M2, and M3 receptor subtypes. By blocking these receptors, it inhibits the parasympathetic nervous system's effects on various organs, leading to decreased glandular secretions (such as saliva, sweat, and gastric acid), slowed heart rate, and relaxation of smooth muscles in the digestive tract and bronchioles.

Glycopyrrolate is available in oral, intravenous, and topical forms and should be used under the supervision of a healthcare professional due to its potential side effects, including dry mouth, blurred vision, dizziness, drowsiness, and urinary retention.

A "knockout" mouse is a genetically engineered mouse in which one or more genes have been deleted or "knocked out" using molecular biology techniques. This allows researchers to study the function of specific genes and their role in various biological processes, as well as potential associations with human diseases. The mice are generated by introducing targeted DNA modifications into embryonic stem cells, which are then used to create a live animal. Knockout mice have been widely used in biomedical research to investigate gene function, disease mechanisms, and potential therapeutic targets.

Enzyme activation refers to the process by which an enzyme becomes biologically active and capable of carrying out its specific chemical or biological reaction. This is often achieved through various post-translational modifications, such as proteolytic cleavage, phosphorylation, or addition of cofactors or prosthetic groups to the enzyme molecule. These modifications can change the conformation or structure of the enzyme, exposing or creating a binding site for the substrate and allowing the enzymatic reaction to occur.

For example, in the case of proteolytic cleavage, an inactive precursor enzyme, known as a zymogen, is cleaved into its active form by a specific protease. This is seen in enzymes such as trypsin and chymotrypsin, which are initially produced in the pancreas as inactive precursors called trypsinogen and chymotrypsinogen, respectively. Once they reach the small intestine, they are activated by enteropeptidase, a protease that cleaves a specific peptide bond, releasing the active enzyme.

Phosphorylation is another common mechanism of enzyme activation, where a phosphate group is added to a specific serine, threonine, or tyrosine residue on the enzyme by a protein kinase. This modification can alter the conformation of the enzyme and create a binding site for the substrate, allowing the enzymatic reaction to occur.

Enzyme activation is a crucial process in many biological pathways, as it allows for precise control over when and where specific reactions take place. It also provides a mechanism for regulating enzyme activity in response to various signals and stimuli, such as hormones, neurotransmitters, or changes in the intracellular environment.

The parotid gland is the largest of the major salivary glands. It is a bilobed, accessory digestive organ that secretes serous saliva into the mouth via the parotid duct (Stensen's duct), located near the upper second molar tooth. The parotid gland is primarily responsible for moistening and lubricating food to aid in swallowing and digestion.

Anatomically, the parotid gland is located in the preauricular region, extending from the zygomatic arch superiorly to the angle of the mandible inferiorly, and from the masseter muscle anteriorly to the sternocleidomastoid muscle posteriorly. It is enclosed within a fascial capsule and has a rich blood supply from the external carotid artery and a complex innervation pattern involving both parasympathetic and sympathetic fibers.

Parotid gland disorders can include salivary gland stones (sialolithiasis), infections, inflammatory conditions, benign or malignant tumors, and autoimmune diseases such as Sjögren's syndrome.

I believe there may be some confusion in your question. "Rabbits" is a common name used to refer to the Lagomorpha species, particularly members of the family Leporidae. They are small mammals known for their long ears, strong legs, and quick reproduction.

However, if you're referring to "rabbits" in a medical context, there is a term called "rabbit syndrome," which is a rare movement disorder characterized by repetitive, involuntary movements of the fingers, resembling those of a rabbit chewing. It is also known as "finger-chewing chorea." This condition is usually associated with certain medications, particularly antipsychotics, and typically resolves when the medication is stopped or adjusted.

Nicotinic antagonists are a class of drugs that block the action of nicotine at nicotinic acetylcholine receptors (nAChRs). These receptors are found in the nervous system and are activated by the neurotransmitter acetylcholine, as well as by nicotine. When nicotine binds to these receptors, it can cause the release of various neurotransmitters, including dopamine, which can lead to rewarding effects and addiction.

Nicotinic antagonists work by binding to nAChRs and preventing nicotine from activating them. This can help to reduce the rewarding effects of nicotine and may be useful in treating nicotine addiction. Examples of nicotinic antagonists include mecamylamine, varenicline, and cytisine.

It's important to note that while nicotinic antagonists can help with nicotine addiction, they can also have side effects, such as nausea, vomiting, and abnormal dreams. Additionally, some people may experience more serious side effects, such as seizures or cardiovascular problems, so it's important to use these medications under the close supervision of a healthcare provider.

In the field of medicine, "time factors" refer to the duration of symptoms or time elapsed since the onset of a medical condition, which can have significant implications for diagnosis and treatment. Understanding time factors is crucial in determining the progression of a disease, evaluating the effectiveness of treatments, and making critical decisions regarding patient care.

For example, in stroke management, "time is brain," meaning that rapid intervention within a specific time frame (usually within 4.5 hours) is essential to administering tissue plasminogen activator (tPA), a clot-busting drug that can minimize brain damage and improve patient outcomes. Similarly, in trauma care, the "golden hour" concept emphasizes the importance of providing definitive care within the first 60 minutes after injury to increase survival rates and reduce morbidity.

Time factors also play a role in monitoring the progression of chronic conditions like diabetes or heart disease, where regular follow-ups and assessments help determine appropriate treatment adjustments and prevent complications. In infectious diseases, time factors are crucial for initiating antibiotic therapy and identifying potential outbreaks to control their spread.

Overall, "time factors" encompass the significance of recognizing and acting promptly in various medical scenarios to optimize patient outcomes and provide effective care.

Trihexyphenidyl is an anticholinergic medication, which is primarily used to treat symptoms of Parkinson's disease, such as rigidity, tremors, muscle spasms, and poor muscle control. It works by blocking the action of acetylcholine, a neurotransmitter in the brain that is involved in the regulation of motor function. By blocking its action, trihexyphenidyl helps to reduce the symptoms of Parkinson's disease.

In addition to its use in Parkinson's disease, trihexyphenidyl may also be used to treat other conditions, such as drug-induced extrapyramidal symptoms (EPS), which are movement disorders that can occur as a side effect of certain medications, including antipsychotic drugs.

It is important to note that trihexyphenidyl can have significant side effects, particularly at higher doses, including dry mouth, blurred vision, dizziness, drowsiness, and difficulty urinating. It may also cause confusion, disorientation, and memory problems, especially in older adults or people with cognitive impairments. As with any medication, trihexyphenidyl should be used under the close supervision of a healthcare provider, who can monitor its effectiveness and potential side effects.

Recombinant proteins are artificially created proteins produced through the use of recombinant DNA technology. This process involves combining DNA molecules from different sources to create a new set of genes that encode for a specific protein. The resulting recombinant protein can then be expressed, purified, and used for various applications in research, medicine, and industry.

Recombinant proteins are widely used in biomedical research to study protein function, structure, and interactions. They are also used in the development of diagnostic tests, vaccines, and therapeutic drugs. For example, recombinant insulin is a common treatment for diabetes, while recombinant human growth hormone is used to treat growth disorders.

The production of recombinant proteins typically involves the use of host cells, such as bacteria, yeast, or mammalian cells, which are engineered to express the desired protein. The host cells are transformed with a plasmid vector containing the gene of interest, along with regulatory elements that control its expression. Once the host cells are cultured and the protein is expressed, it can be purified using various chromatography techniques.

Overall, recombinant proteins have revolutionized many areas of biology and medicine, enabling researchers to study and manipulate proteins in ways that were previously impossible.

Salivation is the process of producing and secreting saliva by the salivary glands in the mouth. It is primarily a reflex response to various stimuli such as thinking about or tasting food, chewing, and speaking. Saliva plays a crucial role in digestion by moistening food and helping to create a food bolus that can be swallowed easily. Additionally, saliva contains enzymes like amylase which begin the process of digesting carbohydrates even before food enters the stomach. Excessive salivation is known as hypersalivation or ptyalism, while reduced salivation is called xerostomia.

Elapid venoms are the toxic secretions produced by elapid snakes, a family of venomous snakes that includes cobras, mambas, kraits, and coral snakes. These venoms are primarily composed of neurotoxins, which can cause paralysis and respiratory failure in prey or predators.

Elapid venoms work by targeting the nervous system, disrupting communication between the brain and muscles. This results in muscle weakness, paralysis, and eventually respiratory failure if left untreated. Some elapid venoms also contain hemotoxins, which can cause tissue damage, bleeding, and other systemic effects.

The severity of envenomation by an elapid snake depends on several factors, including the species of snake, the amount of venom injected, the location of the bite, and the size and health of the victim. Prompt medical treatment is essential in cases of elapid envenomation, as the effects of the venom can progress rapidly and lead to serious complications or death if left untreated.

The vagus nerve, also known as the 10th cranial nerve (CN X), is the longest of the cranial nerves and extends from the brainstem to the abdomen. It has both sensory and motor functions and plays a crucial role in regulating various bodily functions such as heart rate, digestion, respiratory rate, speech, and sweating, among others.

The vagus nerve is responsible for carrying sensory information from the internal organs to the brain, and it also sends motor signals from the brain to the muscles of the throat and voice box, as well as to the heart, lungs, and digestive tract. The vagus nerve helps regulate the body's involuntary responses, such as controlling heart rate and blood pressure, promoting relaxation, and reducing inflammation.

Dysfunction in the vagus nerve can lead to various medical conditions, including gastroparesis, chronic pain, and autonomic nervous system disorders. Vagus nerve stimulation (VNS) is a therapeutic intervention that involves delivering electrical impulses to the vagus nerve to treat conditions such as epilepsy, depression, and migraine headaches.

Mecamylamine is a non-competitive antagonist at nicotinic acetylcholine receptors. It is primarily used in the treatment of hypertension (high blood pressure) that is resistant to other medications, although it has been largely replaced by newer drugs with fewer side effects.

Mecamylamine works by blocking the action of acetylcholine, a neurotransmitter that activates nicotinic receptors and plays a role in regulating blood pressure. By blocking these receptors, mecamylamine can help to reduce blood vessel constriction and lower blood pressure.

It is important to note that mecamylamine can have significant side effects, including dry mouth, dizziness, blurred vision, constipation, and difficulty urinating. It may also cause orthostatic hypotension (a sudden drop in blood pressure when standing up), which can increase the risk of falls and fractures in older adults. As a result, mecamylamine is typically used as a last resort in patients with severe hypertension who have not responded to other treatments.

An oocyte, also known as an egg cell or female gamete, is a large specialized cell found in the ovary of female organisms. It contains half the number of chromosomes as a normal diploid cell, as it is the product of meiotic division. Oocytes are surrounded by follicle cells and are responsible for the production of female offspring upon fertilization with sperm. The term "oocyte" specifically refers to the immature egg cell before it reaches full maturity and is ready for fertilization, at which point it is referred to as an ovum or egg.

Protein binding, in the context of medical and biological sciences, refers to the interaction between a protein and another molecule (known as the ligand) that results in a stable complex. This process is often reversible and can be influenced by various factors such as pH, temperature, and concentration of the involved molecules.

In clinical chemistry, protein binding is particularly important when it comes to drugs, as many of them bind to proteins (especially albumin) in the bloodstream. The degree of protein binding can affect a drug's distribution, metabolism, and excretion, which in turn influence its therapeutic effectiveness and potential side effects.

Protein-bound drugs may be less available for interaction with their target tissues, as only the unbound or "free" fraction of the drug is active. Therefore, understanding protein binding can help optimize dosing regimens and minimize adverse reactions.

Nicotinic receptors are a type of ligand-gated ion channel receptor that are activated by the neurotransmitter acetylcholine and the alkaloid nicotine. They are widely distributed throughout the nervous system and play important roles in various physiological processes, including neuronal excitability, neurotransmitter release, and cognitive functions such as learning and memory. Nicotinic receptors are composed of five subunits that form a ion channel pore, which opens to allow the flow of cations (positively charged ions) when the receptor is activated by acetylcholine or nicotine. There are several subtypes of nicotinic receptors, which differ in their subunit composition and functional properties. These receptors have been implicated in various neurological disorders, including Alzheimer's disease, Parkinson's disease, and schizophrenia.

Phosphorylation is the process of adding a phosphate group (a molecule consisting of one phosphorus atom and four oxygen atoms) to a protein or other organic molecule, which is usually done by enzymes called kinases. This post-translational modification can change the function, localization, or activity of the target molecule, playing a crucial role in various cellular processes such as signal transduction, metabolism, and regulation of gene expression. Phosphorylation is reversible, and the removal of the phosphate group is facilitated by enzymes called phosphatases.

Hexamethonium is defined as a ganglionic blocker, which is a type of medication that blocks the activity at the junction between two nerve cells (neurons) called the neurotransmitter receptor site. It is a non-depolarizing neuromuscular blocking agent, which means it works by binding to and inhibiting the action of the nicotinic acetylcholine receptors at the motor endplate, where the nerve meets the muscle.

Hexamethonium was historically used in anesthesia practice as a adjunct to provide muscle relaxation during surgical procedures. However, its use has largely been replaced by other neuromuscular blocking agents that have a faster onset and shorter duration of action. It is still used in research settings to study the autonomic nervous system and for the treatment of hypertensive emergencies in some cases.

It's important to note that the use of Hexamethonium requires careful monitoring and management, as it can have significant effects on cardiovascular function and other body systems.

Neostigmine is a medication that belongs to a class of drugs called cholinesterase inhibitors. It works by blocking the breakdown of acetylcholine, a neurotransmitter in the body, leading to an increase in its levels at the neuromuscular junction. This helps to improve muscle strength and tone by enhancing the transmission of nerve impulses to muscles.

Neostigmine is primarily used in the treatment of myasthenia gravis, a neurological disorder characterized by muscle weakness and fatigue. It can also be used to reverse the effects of non-depolarizing muscle relaxants administered during surgery. Additionally, neostigmine may be used to diagnose and manage certain conditions that cause decreased gut motility or urinary retention.

It is important to note that neostigmine should be used under the close supervision of a healthcare professional due to its potential side effects, which can include nausea, vomiting, diarrhea, increased salivation, sweating, and muscle cramps. In some cases, it may also cause respiratory distress or cardiac arrhythmias.

Sympathetic ganglia are part of the autonomic nervous system, which controls involuntary bodily functions. These ganglia are clusters of nerve cell bodies located outside the central nervous system, along the spinal cord. They serve as a relay station for signals sent from the central nervous system to the organs and glands. The sympathetic ganglia are responsible for the "fight or flight" response, releasing neurotransmitters such as norepinephrine that prepare the body for action in response to stress or danger.

Choline O-Acetyltransferase (COAT, ChAT) is an enzyme that plays a crucial role in the synthesis of the neurotransmitter acetylcholine. It catalyzes the transfer of an acetyl group from acetyl CoA to choline, resulting in the formation of acetylcholine. Acetylcholine is a vital neurotransmitter involved in various physiological processes such as memory, cognition, and muscle contraction. COAT is primarily located in cholinergic neurons, which are nerve cells that use acetylcholine to transmit signals to other neurons or muscles. Inhibition of ChAT can lead to a decrease in acetylcholine levels and may contribute to neurological disorders such as Alzheimer's disease and myasthenia gravis.

Tropane alkaloids are a class of naturally occurring compounds that contain a tropane ring in their chemical structure. This ring is composed of a seven-membered ring with two nitrogen atoms, one of which is part of a piperidine ring. Tropane alkaloids are found in various plants, particularly those in the Solanaceae family, which includes nightshade, belladonna, and datura. Some well-known tropane alkaloids include atropine, scopolamine, and cocaine. These compounds have diverse pharmacological activities, such as anticholinergic, local anesthetic, and central nervous system stimulant effects.

Phenylpropanolamine is a decongestant and appetite suppressant that has been used in over-the-counter and prescription medications. It works by narrowing blood vessels in the nose, which can help to relieve nasal congestion. As an appetite suppressant, it is thought to work by affecting certain chemicals in the brain that control appetite.

However, phenylpropanolamine has been associated with an increased risk of hemorrhagic stroke (bleeding in the brain) and other cardiovascular events, particularly in women who are otherwise healthy but have a history of high blood pressure or smoking. As a result, the U.S. Food and Drug Administration (FDA) advised manufacturers to stop selling over-the-counter products containing phenylpropanolamine in 2005.

It is important to note that this substance should only be used under the supervision of a healthcare professional, and individuals should always follow their doctor's instructions carefully when taking any medication.

Electrophysiology is a branch of medicine that deals with the electrical activities of the body, particularly the heart. In a medical context, electrophysiology studies (EPS) are performed to assess abnormal heart rhythms (arrhythmias) and to evaluate the effectiveness of certain treatments, such as medication or pacemakers.

During an EPS, electrode catheters are inserted into the heart through blood vessels in the groin or neck. These catheters can record the electrical activity of the heart and stimulate it to help identify the source of the arrhythmia. The information gathered during the study can help doctors determine the best course of treatment for each patient.

In addition to cardiac electrophysiology, there are also other subspecialties within electrophysiology, such as neuromuscular electrophysiology, which deals with the electrical activity of the nervous system and muscles.

Overactive bladder (OAB) is a urological condition characterized by the involuntary contraction of the detrusor muscle of the urinary bladder, leading to symptoms such as urgency, frequency, and nocturia (the need to wake up at night to urinate), with or without urge incontinence (the involuntary loss of urine associated with a strong desire to void). It is important to note that OAB is not necessarily related to bladder volume or age-related changes, and it can significantly impact an individual's quality of life. The exact cause of OAB is not fully understood, but it may be associated with neurological disorders, certain medications, infections, or other underlying medical conditions. Treatment options for OAB include behavioral modifications, pelvic floor exercises, bladder training, medications, and, in some cases, surgical interventions.

Acetylcholinesterase (AChE) is an enzyme that catalyzes the hydrolysis of acetylcholine (ACh), a neurotransmitter, into choline and acetic acid. This enzyme plays a crucial role in regulating the transmission of nerve impulses across the synapse, the junction between two neurons or between a neuron and a muscle fiber.

Acetylcholinesterase is located in the synaptic cleft, the narrow gap between the presynaptic and postsynaptic membranes. When ACh is released from the presynaptic membrane and binds to receptors on the postsynaptic membrane, it triggers a response in the target cell. Acetylcholinesterase rapidly breaks down ACh, terminating its action and allowing for rapid cycling of neurotransmission.

Inhibition of acetylcholinesterase leads to an accumulation of ACh in the synaptic cleft, prolonging its effects on the postsynaptic membrane. This can result in excessive stimulation of cholinergic receptors and overactivation of the cholinergic system, which may cause a range of symptoms, including muscle weakness, fasciculations, sweating, salivation, lacrimation, urination, defecation, bradycardia, and bronchoconstriction.

Acetylcholinesterase inhibitors are used in the treatment of various medical conditions, such as Alzheimer's disease, myasthenia gravis, and glaucoma. However, they can also be used as chemical weapons, such as nerve agents, due to their ability to disrupt the nervous system and cause severe toxicity.

The superior cervical ganglion is a part of the autonomic nervous system, specifically the sympathetic division. It is a collection of nerve cell bodies (ganglion) that are located in the neck region (cervical) and is formed by the fusion of several smaller ganglia.

This ganglion is responsible for providing innervation to various structures in the head and neck, including the eyes, scalp, face muscles, meninges (membranes surrounding the brain and spinal cord), and certain glands such as the salivary and sweat glands. It does this through the postganglionic fibers that branch off from the ganglion and synapse with target organs or tissues.

The superior cervical ganglion is an essential component of the autonomic nervous system, which controls involuntary physiological functions such as heart rate, blood pressure, digestion, and respiration.

The muscarinic acetylcholine receptor M2, also known as the cholinergic receptor, muscarinic 2, is a muscarinic acetylcholine ... Both M2 and M3 muscarinic receptors are expressed in the smooth muscles of the airway, with the majority of the receptors being ... "Acetylcholine receptors (muscarinic): M2". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and ... "Entrez Gene: CHRM2 cholinergic receptor, muscarinic 2". Hirshman CA, Lande B, Croxton TL (January 1999). "Role of M2 muscarinic ...
... inactive at M2 and M4. ML375 VU6008667 VU-0488130 (ML381) Xanomeline Diphenhydramine Muscarinic acetylcholine receptor GRCh38: ... The human muscarinic acetylcholine receptor M5, encoded by the CHRM5 gene, is a member of the G protein-coupled receptor ... "Phosphorylation of human m1 muscarinic acetylcholine receptors by G protein-coupled receptor kinase 2 and protein kinase C". ... G protein-coupled receptors, Human proteins, Muscarinic acetylcholine receptors). ...
... is also an M2 receptor muscarinic agonist. Digoxin is usually given orally, but can also be given by IV injection in ... Digoxin has the ability to bind oestrogen receptors, and therefore it has been proposed that it might increase the risk of ...
... is a competitive muscarinic receptor antagonist that is relatively selective at the M2 receptor. It was investigated ... The (+)-enantiomer has 8 times greater potency at the M2 receptor than the (-)-enantiomer. Muscarinic antagonist Antiarrhythmic ... Buckley NJ, Bonner TI, Buckley CM, Brann MR (1989). "Antagonist binding properties of five cloned muscarinic receptors ...
Gallamine triethiodide M2 receptor Muscarinic receptor Acetylcholine Jakubík J, Zimčík P, Randáková A, Fuksová K, El-Fakahany ... Watson N, Barnes PJ, Maclagan J (January 1992). "Actions of methoctramine, a muscarinic M2 receptor antagonist, on muscarinic ... It preferentially binds to the pre-synaptic receptor M2, a muscarinic acetylcholine ganglionic protein complex present ... "Methoctramine selectively blocks cardiac muscarinic M2 receptors in vivo". Naunyn-Schmiedeberg's Archives of Pharmacology. 338 ...
M2 muscarinic receptor antagonism". Anesthesiology. 98 (4): 906-911. doi:10.1097/00000542-200304000-00017. PMID 12657852. S2CID ... Cardone C, Szenohradszky J, Yost S, Bickler PE (May 1994). "Activation of brain acetylcholine receptors by neuromuscular ... and opioid subtype receptors: implication for laudanosine seizure activity". Brain Research. 646 (2): 235-241. doi:10.1016/0006 ... owing to accumulation of cytosolic calcium caused by activation of acetylcholine receptor ion channels. Unlike the two ...
M2 muscarinic receptors act via a Gi type receptor, which causes a decrease in cAMP in the cell, inhibition of voltage-gated ... The receptors m1 and m2 were determined based upon partial sequencing of M1 and M2 receptor proteins. The others were found by ... Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in ... Acetylcholine Receptors (Muscarinic) Receptors,+Muscarinic at the U.S. National Library of Medicine Medical Subject Headings ( ...
Atropine acts on the M2 receptors of the heart and antagonizes the activity of acetylcholine. It causes tachycardia by blocking ... is a type of anticholinergic agent that blocks the activity of the muscarinic acetylcholine receptor. The muscarinic receptor ... Certain muscarinic antagonists can be classified into either long-acting muscarinic receptor antagonists (LAMAs) or short- ... Effects of Muscarinic Antagonist Atropine (Muscarinic Receptor Antagonist), Cardiovascular Pharmacology Concepts, Richard E. ...
Teaktong T, Piggott MA, Mckeith IG, Perry RH, Ballard CG, Perry EK (June 2005). "Muscarinic M2 and M4 receptors in anterior ... The muscarinic acetylcholine receptor M4, also known as the cholinergic receptor, muscarinic 4 (CHRM4), is a protein that, in ... Activation of M4 receptors inhibits acetylcholine release in the striatum. The M2 subtype of acetylcholine receptor functions ... Muscarinic acetylcholine receptors possess a regulatory effect on dopaminergic neurotransmission. Activation of M4 receptors in ...
... is an antimuscarinic agent that nonselectively antagonizes muscarinic acetylcholine receptors, M1 and M2. Bornaprine ... When administered to healthy humans, bornaprine suppressed the amount of REM sleep, suggesting that the M1 and M2 receptors are ... Bornaprine also has a pa2 value (affinity of antagonist for receptor) of 7.27 ± 0.21 indicating a high potency. Bornaprine is ...
... derived from the M4 muscarinic receptor that couples with the Gi protein. Another Gi coupled human muscarinic receptor, M2, was ... derived from muscarinic or κ-opioid receptors. One of the first DREADDs was based on the human M3 muscarinic receptor (hM3). ... M1 and M5 muscarinic receptors have been mutated to create DREADDs hM1Dq and hM5Dq respectively. The most commonly used ... These receptors are also known as GsD and are chimeric receptors containing intracellular regions of the turkey erythrocyte β- ...
Vagal stimulation of the myocardium, specifically, is mediated by M2-subtype muscarinic acetylcholine receptors (mAChR). In ... of approximately 10 μM and binds the group II receptor site located on segment 6 of domains I and IV (IS6 and IVS6). Other ... severe cases of grayanotoxin poisoning, atropine (a non-specific "mAChR antagonist" or Muscarinic antagonist) can be used to ...
June 2017). "Novel bipharmacophoric inhibitors of the cholinesterases with affinity to the muscarinic receptors M1 and M2". ... The remaining 5-10% of the succinylcholine dose acts as an acetylcholine receptor agonist at the neuromuscular junction, ... Pseudocholinesterase deficiency can result in higher levels of intact succinylcholine molecules reaching receptors in the ... membrane of the motor neuron does not produce any additional change in membrane potential after binding to its receptor on the ...
... with selectivity for the M2 and M4 subtypes. It is used mainly for mapping the distribution of M2 and M4 muscarinic receptors ... Zavitsanou K, Katsifis A, Yu Y, Huang XF (May 2005). "M2/M4 muscarinic receptor binding in the anterior cingulate cortex in ... Teaktong T, Piggott MA, Mckeith IG, Perry RH, Ballard CG, Perry EK (June 2005). "Muscarinic M2 and M4 receptors in anterior ... a selective antagonist of muscarinic M2 receptors". Bioorganic & Medicinal Chemistry. 8 (3): 591-600. doi:10.1016/S0968-0896(99 ...
June 2017). "Novel bipharmacophoric inhibitors of the cholinesterases with affinity to the muscarinic receptors M1 and M2". ... Hyperstimulation of nicotinic and muscarinic receptors. When used in the central nervous system to alleviate neurological ... This results in continuous activation of acetylcholine receptors, which leads to the acute symptoms of TEPP poisoning. The ... also an adenosine receptor antagonist) Rosmarinic acid - ester of caffeic acid. Found in plants species of family Lamiaceae. ...
Myslivecek J, Klein M, Novakova M, Ricny J (July 2008). "The detection of the non-M2 muscarinic receptor subtype in the rat ... a novel muscarinic M4 receptor antagonist, discriminates between striatal and cortical muscarinic receptors coupled to cyclic ... PD-102,807 is a drug which acts as a selective antagonist for the muscarinic acetylcholine receptor M4. It is used in ... Hogan K, Markos F (February 2007). "Muscarinic type 1 receptors mediate part of nitric oxide's vagal facilitatory effect in the ...
Peripheral muscarinic receptors are part of the autonomic nervous system. M2 receptors are located in the brain and heart, M3 ... Scopolamine is a nonspecific muscarinic antagonist at all four (M1, M2, M3, and M4) receptor sites. Due to these compounds' ... Particularly the M1 muscarinic receptor. M1 receptors are located primarily in the central nervous system and are involved in ... Delirium is only associated with the antagonism of post‐synaptic M1 receptors and to date other receptor subtypes have not been ...
ACh binds to a receptor called an M2 muscarinic receptor, located on the SA node membrane. Activation of this M2 receptor then ... This binds to a receptor on the SA node membrane, called a beta-1adrenoceptor. Binding of NA to this receptor activates a G- ...
... since they are not fully selective for the nicotinic receptor and hence may have effects on muscarinic receptors. If nicotinic ... Pancuronium and some other neuromuscular blocking agents block M2-receptors and therefore affect the vagus nerve, leading to ... Each ACh-receptor has two receptive sites and activation of the receptor requires binding to both of them. Each receptor site ... Beers and Reich's studies on cholinergic receptors in 1970 showed a relationship affecting whether a compound was muscarinic or ...
Other: Experimental studies observed that activating autoantibodies to the beta1/2-adrenergic and M2 muscarinic receptors are ... "Activating autoantibodies to the beta-1 adrenergic and m2 muscarinic receptors facilitate atrial fibrillation in patients with ... "Activating autoantibodies to the beta1-adrenergic and M2 muscarinic receptors facilitate atrial fibrillation in patients with ... "Activating autoantibodies to the β1/2-adrenergic and M2 muscarinic receptors associate with atrial tachyarrhythmias in patients ...
"Reduction in choline acetyltransferase immunoreactivity but not muscarinic-m2 receptor immunoreactivity in the brainstem of ... Braida D, Ponzoni L, Martucci R, Sparatore F, Gotti C, Sala M (May 2014). "Role of neuronal nicotinic acetylcholine receptors ( ...
"Differential roles of M2 and M3 muscarinic receptor subtypes in modulation of bladder afferent activity in rats". Urology. 75 ( ... Dimetindene is also an M2 receptor antagonist. It was patented in 1958 and came into medical use in 1960. Dimetindene is used ... Articles with short description, Short description matches Wikidata, ECHA InfoCard ID from Wikidata, H1 receptor antagonists, ... "The suppression of olfactory bulbectomy-induced muricide by antidepressants and antihistamines via histamine H1 receptor ...
... 's activity as a muscarinic receptor antagonist, with specificity for the muscarinic acetylcholine receptor M2, made ... "Himbacine analogs as muscarinic receptor antagonists-effects of tether and heterocyclic variations". Bioorganic & Medicinal ... The development of a muscarinic antagonist based on himbacine failed but an analog, vorapaxar, has been approved by the FDA as ... 2008). "Discovery of a Novel, Orally Active Himbacine-Based Thrombin Receptor Antagonist (SCH 530348) with Potent Antiplatelet ...
Pancuronium: Pancuronium produces more significant adverse effects due to the blockade of muscarinic M2 receptors in the atria ... Secondly, succinylcholine causes the activation of muscarinic receptors in the SA node, causing bradycardia. This effect is ... H1 and H2 receptor blocking agents can be used to attenuate the drop in mean arterial pressure. A slow injection speed between ... These nicotinic receptors respond to acetylcholine and are located in the central and peripheral nervous system, muscle, and ...
... such as those at muscarinic M2 receptors tested as analgesics or antiproliferative drugs, or those at opioid receptors that ... "Activation of M2 muscarinic acetylcholine receptors by a hybrid agonist enhances cytotoxic effects in GB7 glioblastoma cancer ... One notable example of functional selectivity occurs with the 5-HT2A receptor, as well as the 5-HT2C receptor. Serotonin, the ... Kenakin T (1995). "Agonist-Receptor Efficacy. II. Agonist Trafficking of Receptor Signals". Trends Pharmacol Sci. 16 (7): 232-8 ...
"Acidic amino acids flanking phosphorylation sites in the M2 muscarinic receptor regulate receptor phosphorylation, ... 1999). "Role of the T cell receptor alpha chain in stabilizing TCR-superantigen-MHC class II complexes". Immunity. 10 (4): 473- ... 1995). "Chromosome mapping of the human arrestin (SAG), beta-arrestin 2 (ARRB2), and beta-adrenergic receptor kinase 2 (ADRBK2 ... 1996). "Effect of different G protein-coupled receptor kinases on phosphorylation and desensitization of the alpha1B-adrenergic ...
In particular, the activation of muscarinic acetylcholine receptor M2 and muscarinic acetylcholine receptor M4 inhibits ... CB1 receptors formed homodimers, and they also heterodimerized with both orexin receptors. ... In conclusion, orexin receptors ... The 5-HT2A receptors expressed on dopaminergic neurons increase activity, while 5-HT2C receptors elicit a decrease in activity ... As orexin receptors efficiently signal via endocannabinoid production to CB1 receptors, dimerization could be an effective way ...
Acetylcholine then binds to M2 muscarinic receptors, causing the decrease in heart rate that is referred to as reflex ... The M2 muscarinic receptors decrease the heart rate by inhibiting depolarization of the sinoatrial node via Gi protein-coupled ... receptors and through modulation of muscarinic potassium channels. Additionally, M2 receptors reduce the contractile forces of ... M2 receptors have no effect on the contractile forces of the ventricular muscle. Stimuli causing reflex bradycardia include: ...
The lead compound contained a piperazine scaffold and was a potent muscarinic acetylcholine receptor (M2) antagonist with ... CCR5 receptor antagonists are a class of small molecules that antagonize the CCR5 receptor. The C-C motif chemokine receptor ... Vicriviroc had an excellent selectivity for CCR5 receptors over muscarinic and hERG affinity was greatly reduced. Phase I ... R5 strain is when the virus uses the co-receptor CCR5 and X4 strain is when it uses CXCR4. The location of CCR5 receptors at ...
Muscarinic receptors form G protein-coupled receptor complexes in the cell membranes of neurons and other cells. Atropine is a ... The M2 and M4 subtypes are Gi/Go-coupled; they decrease intracellular levels of cAMP by inhibiting adenylate cyclase. Their ... It is estimated that the nicotinic receptor family dates back longer than 2.5 billion years. Likewise, muscarinic receptors are ... The two major types of acetylcholine receptors, muscarinic and nicotinic receptors, have convergently evolved to be responsive ...
Migeon JC, Thomas SL, Nathanson NM (Jul 1995). "Differential coupling of m2 and m4 muscarinic receptors to inhibition of ... "The human thyrotropin receptor: a heptahelical receptor capable of stimulating members of all four G protein families". ... Lee MJ, Evans M, Hla T (May 1996). "The inducible G protein-coupled receptor edg-1 signals via the G(i)/mitogen-activated ... Lee MJ, Evans M, Hla T (May 1996). "The inducible G protein-coupled receptor edg-1 signals via the G(i)/mitogen-activated ...
The muscarinic acetylcholine receptor M2, also known as the cholinergic receptor, muscarinic 2, is a muscarinic acetylcholine ... Both M2 and M3 muscarinic receptors are expressed in the smooth muscles of the airway, with the majority of the receptors being ... "Acetylcholine receptors (muscarinic): M2". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and ... "Entrez Gene: CHRM2 cholinergic receptor, muscarinic 2". Hirshman CA, Lande B, Croxton TL (January 1999). "Role of M2 muscarinic ...
The effect of antigen challenge on the function of neuronal M2-muscarinic autoreceptors in the lungs was studied in ... Dysfunction of M2-muscarinic receptors in pulmonary parasympathetic nerves after antigen challenge J Appl Physiol (1985). 1991 ... attenuated vagally induced bronchoconstriction by stimulating inhibitory M2-muscarinic receptors on parasympathetic nerves in ... The effect of antigen challenge on the function of neuronal M2-muscarinic autoreceptors in the lungs was studied in ...
Our new paper: On homology modeling of the M2 muscarinic acetylcholine receptor subtype. Model of M2 receptor from side- (left ... Introduction Laboratory of Neurochemistry Our new paper: On homology modeling of the M2 muscarinic acetylcholine receptor ... Twelve homology models of the human M2 muscarinic receptor using different sets of templates have been designed using the Prime ... the M3 muscarinic receptor (PDB:4DAJ). Adding more (structurally distant) templates led to worse models. Data document a key ...
7tmA_mAChR_M2; muscarinic acetylcholine receptor subtype M2, member of the class A family of seven-transmembrane G protein- ... 7tmA_mAChR_M2; muscarinic acetylcholine receptor subtype M2, member of the class A family of seven-transmembrane G protein- ... 7tmA_mAChR_M2; muscarinic acetylcholine receptor subtype M2, member of the class A family of seven-transmembrane G protein- ... 7tmA_mAChR_M2; muscarinic acetylcholine receptor subtype M2, member of the class A family of seven-transmembrane G protein- ...
... is no evidence suggesting that hyperresponsiveness results from any alterations in function of these M3 muscarinic receptors. ... Contraction of airway smooth muscle is mediated by M3 muscarinic receptors on the airway smooth muscle. However, there ... Release of acetylcholine is controlled by inhibitory M2 muscarinic receptors, and it appears that it is these M2 receptors that ... In conclusion, loss of function of inhibitory M2 muscarinic receptors on the airway parasympathetic nerves causes vagally ...
In this study muscarinic receptor expression, namely M2 and M3 subtypes of muscarinic receptors were analyzed on bladder tumor ... Specifically M2 and M3 type receptors are the most common receptors of bladder. M2 receptors are specially found on umbrella ... M2 and M3 muscarinic receptors not only play a great role on bladder functions but also also may be important for bladder ... Progression rate was found higher in patients with higher M2 muscarinic receptor levels on bladder tissue samples. ...
Receptor Legislation Assay. CHO-M1 -M2 or -M3 cells had been seeded at 75 0 cells per well in 24-well plates for 24 h before ... A fresh class of subtype-selective muscarinic acetylcholine (mACh) receptor agonist that activates the receptor through ... A fresh class of subtype-selective muscarinic acetylcholine (mACh) receptor agonist that. ... Outcomes Perseverance of Agonist Binding Affinities in M1 M3 and M2 mACh Receptors. [3H]NMS saturation binding tests had been ...
M2-muscarinic receptor subtype 2; M3-muscarinic receptor subtype 3; NO-nitric oxide; P2X1-purinergic receptor P2X, ligand-gated ... M2-muscarinic receptor subtype 2; M3-muscarinic receptor subtype 3; NO-nitric oxide; P2X1-purinergic receptor P2X, ligand-gated ... The role of the M2 muscarinic receptor subtype in the human bladder is not well established. Data from small studies ... Chapple CR, Yamanishi T, Chess-Williams R. Muscarinic receptor subtypes and management of the overactive bladder. Urology. 2002 ...
T1 - Muscarinic receptor M2 in cat visual cortex. T2 - Laminar distribution, relationship to GABAergic neurons and effect of ... Muscarinic receptor M2 in cat visual cortex: Laminar distribution, relationship to GABAergic neurons and effect of cingulate ... Muscarinic receptor M2 in cat visual cortex: Laminar distribution, relationship to GABAergic neurons and effect of cingulate ... title = "Muscarinic receptor M2 in cat visual cortex: Laminar distribution, relationship to GABAergic neurons and effect of ...
Selective muscarinic M2 and M3 receptor antagonist. 40-68. bd, twice daily; od, once daily; qds, four times daily; tds, three ... Selective muscarinic M3 receptor antagonist. 3.1. Solifenacin succinate. Vesicare® (Yamanouchi Pharma Ltd, West Byfleet, UK). 5 ... Receptor subtype selectivity. Elimination half-life of parent drug (h). Propantheline bromide. Pro-Banthine® (Concord ...
... other neurotransmitter receptors, and indices of cell signaling and cell damage. Nicotine evoked nAChR upregulation, but with ... indicate that nicotine is a neuroteratogen that disrupts brain development by stimulating nicotinic acetylcholine receptors ( ... Migeon JC, Thomas SL, Nathanson NM (1995). Differential coupling of m2 and m4 muscarinic receptors to inhibition of adenylyl ... β-adrenergic and m2-muscarinic receptors and their linkage to adenylyl cyclase. Brain Res 878: 119-126. ...
During CMG, M2 selective muscarinic receptor antagonist (methoctramine) and nonselective muscarinic receptor antagonist ( ... and by M2 and M3 muscarinic receptors in urothelium. It seems to need to ascertain the existence of M2 and M3 muscarinic ... The Role of Muscarinic Receptor Subtype on Detrusor Overactivity induced by Bladder Outlet Obstruction in Rats .utlogo1 { ... We studied the role of muscarinic receptor subtype on urothelium and detrusor in rats with detrusor overactivity induced by ...
In contrast to atropine, THP more selectively inhibits M1 and M3 than M2 mAChRs. In addition, THP inhibits as-of-yet ... Treatment relies heavily on the use of high doses of atropine to block muscarinic receptor overactivation by acetylcholine (ACh ... Although rarely taken into account, the non-selective inhibition of all muscarinic receptor (mAChR) subtypes by atropine may be ... Thus, this project will test the hypothesis that, in part by sparing M2 mAChRs and potentially by blocking nAChRs in addition ...
Gαi also couples many receptors to PI-PLC. These include the m2 muscarinic receptor, thrombin, metabotropic glutamate, α2- ... 1993) Transfected m2 muscarinic acetylcholine receptors couple to Gαi2 and Gαi3 in chinese hamster ovary cells. J Biol Chem 268 ... 1997) Localization of calcium receptor mRNA in the adult rat central nervous system by in situ hybridization. Brain Res 744:47- ... 1998) Calcium receptor activation potentiates spike after-polarizations in rat subfornical organ neurons. Soc Neurosci Abstr 24 ...
Subcelular localization of m2 muscarinic receptor in GABAergic interneurons of the olfactory bulb. European Journal of ... Perez-Rando M; Castillo-Gómez E; Guirado R; Blasco-Ibañez JM; Crespo C; Varea E; Nacher J (2017) NMDA Receptors Regulate the ... Bellés M; Carbonell J; Blasco-Ibáñez JM; Crespo C; Nácher J; Varea E (2019) Alterations in reelin and reelin receptors in Down ... Castillo-Gómez E; Varea E; Blasco-Ibáñez JM; Crespo C; Nacher J. (2011) Polysialic Acid is required for dopamine d2 receptor- ...
Positive cooperativity induced by alcuronium appears to be specific for the m2 (cardiac) subtype of muscarinic receptors. ... Positive cooperativity in the binding of alcuronium and N-methylscopolamine to muscarinic acetylcholine receptors.. S Tucek, J ... Positive cooperativity in the binding of alcuronium and N-methylscopolamine to muscarinic acetylcholine receptors.. S Tucek, J ... Positive cooperativity in the binding of alcuronium and N-methylscopolamine to muscarinic acetylcholine receptors.. S Tucek, J ...
Then, what makes dif-ferences between M2 and M2 ? It is possible that M2 and M2 come from dif-ferent modification of receptor ... We called them M2 with higher affinity for the agonists and M2 with the lower affinity. M2 couples with inhibition of adenylate ... Cardiac maCh-R (M2 subtype) are thought to consist of a single species of receptor protein. We analyzed the binding ... Four subtypes (M1-M4) in muscarinic receptors (mACh-R) were discovered by the method of gene technology. But, three of them are ...
Muscarinic acetylcholine receptors. M1, M3, M5 receptors are coupled with Gq proteins, while M2 and M4 receptors are coupled ... Acetylcholine Receptors. Nicotinic acetylcholine receptors. *Nicotinic Acetylcholine Receptors in general The receptor is a ... The H1 receptor is a histamine receptor belonging to the family of rhodopsin-like G-protein-coupled receptors. The H1 receptor ... Glutamate receptor (GluA2) Metabotropic Glutamate Receptors. Metabotropic glutamate receptors are glutamate receptors that ...
... is known to inhibit some voltage-dependent ion channels and muscarinic receptors, but its interaction with ligand-gated ion ... We have studied if Pm affects nicotinic acetylcholine receptors (nAChRs), since they play broad functional roles, both in the ... M2 muscarinic receptor inhibition, which might account for asthma amelioration, since M2 receptors are involved in airway ... of five alkaloids from bulbus fritillariae on the concentration of cAMP in HEK cells transfected with muscarinic M2 receptor ...
Coupling of M2 muscarinic receptors to Src activation in cultured canine colonic smooth muscle cells ...
... the ionotropic nicotinic receptor (nAChR) and the G-protein-coupled muscarinic receptor (mAChR). To determine which type of ... it is known that Gi/o-linked M2/M4 receptors cause presynaptic inhibition of voltage-gated Ca2+ channels, whereas Gq/11-linked ... Muscarinic and nicotinic ACh receptors are widely expressed in the hippocampus, and upon activation by ACh can modulate ... Muscarinic acetylcholine receptors (mAChRs) in the nervous system: Some functions and mechanisms. J Mol Neurosci 2010, 41: 340- ...
M2, M3 receptor antagonist; and NLS-12, a norepinephrine and dopamine reuptake inhibitor and muscarinic M4 receptor antagonist ... a melatonin ML1A receptor agonist, improved scopolamine-induced amnesia; NLS-11, a norepinephrine and dopamine reuptake ...
A single kinetic step in the G protein activation cycle determines whether a G protein-coupled receptor activates G protein- ... Interactions of agonists with M2 and M4 muscarinic receptor subtypes mediating cyclic AMP inhibition ... 1984) Mode of regulation of the ACh-sensitive K-channel by the muscarinic receptor in rabbit atrial cells Pflügers Archiv ... Stimulated muscarinic acetylcholine receptors (M2Rs) release Gβγ subunits, which slow heart rate by activating a G protein- ...
Optimization of ligands for the muscarinic m2 receptor. +49 30 838 53249 ... The impact of natural receptor variants and opioid metabolites on µ-opioid receptor function. ... Machine learning models as an approach to differentiate conformational states of G-protein-coupled receptors ... Structural Basis of Opioid Peptide Binding to the Atypical Chemokine Receptor 3 (ACKR3) ...
... while the M2 and M4 AChR may have an opposite effect, this may explain why treatment with cholinesterase inhibitors lack an ... but it has been difficult to pin the effect on a specific receptor subtype: There are five different muscarinic receptors (M1- ... Deletion of M1 muscarinic acetylcholine receptors increases amyloid pathology in vitro and in vivo. J Neurosci. 2010 Mar 24;30( ... The muscarinic acetylcholine receptor has been a target for AD therapies for decades, based first on the loss of acetylcholine ...
... discovery of selective positive allosteric modulators of antagonists for the M2 muscarinic acetylcholine receptor. Proc Natl ... Muscarinic receptors as model targets and antitargets for structure-based ligand discovery. Mol Pharmacol. 2013 Oct; 84(4):528- ... Structure-guided development of selective M3 muscarinic acetylcholine receptor antagonists. Proc Natl Acad Sci U S A. 2018 11 ... Structure-Based Design and Discovery of New M2 Receptor Agonists. J Med Chem. 2017 11 22; 60(22):9239-9250. ...
Potent and selective M2 muscarinic receptor antagonist €125.00 3513 Bethanechol chloride Muscarinic receptor (mAChR) agonist € ... Muscarinic receptor (mAChR) antagonist €60.00 3648 Trospium chloride Specific, orally active and competitive muscarinic ... Unlike the nicotinergic acetylcholine receptor, the muscarinic type is part of the family of G-protein coupled receptors (GPCR- ... 4] Cloning and Expression of the Human and Rat m5 Muscarinic Acetylcholine Receptor Genes. Bonner, T. I.; Young, A. C.; Brann, ...
This includes actions on 5-HT receptors and muscarinic receptors (including M2 receptors focused on in this study; Jendryka et ... 2019) Balanced cholinergic modulation of spinal locomotor circuits via M2 and M3 muscarinic receptors Scientific Reports 9: ... H. U. M2, M3 and M4, but not M1, muscarinic receptor subtypes are present in rat spinal cord ... Previous work indicated that activation of M2 receptors in spinal cord slices increases motor output through M2 receptor- ...
M2) affinity binding sites for PZ occurs, incubation of cerebral cortical membranes with PBCM in the presence of PZ should not ... was used to protect muscarinic receptors from blockade by the irreversible muscarinic receptor antagonist propylbenzilylcholine ... Muscarinic cholinergic receptor binding sites differentiated by their affinity for pirenzepine do not interconvert.. D W Gil ... Muscarinic cholinergic receptor binding sites differentiated by their affinity for pirenzepine do not interconvert.. D W Gil ...
  • Conversely, blockade of these receptors with the antagonist gallamine (0.1-10 mg/kg iv) produced a marked potentiation of vagally induced bronchoconstriction. (nih.gov)
  • During CMG, M2 selective muscarinic receptor antagonist (methoctramine) and nonselective muscarinic receptor antagonist (tolterodine) were administrated intravesically. (urotoday.com)
  • and NLS-12, a norepinephrine and dopamine reuptake inhibitor and muscarinic M4 receptor antagonist. (yahoo.com)
  • To test the hypothesis that the putative muscarinic receptor subtypes in rat forebrain are interconvertible states of the same receptor, the selective antagonist pirenzepine (PZ) was used to protect muscarinic receptors from blockade by the irreversible muscarinic receptor antagonist propylbenzilylcholine mustard (PBCM). (aspetjournals.org)
  • Such effect was completely reversed both by the opioid receptor antagonist naloxone and by the unselective muscarinic receptor antagonist atropine. (researchgate.net)
  • The muscarinic acetylcholine receptor M2, also known as the cholinergic receptor, muscarinic 2, is a muscarinic acetylcholine receptor that in humans is encoded by the CHRM2 gene. (wikipedia.org)
  • 8. Melchiorre C., Bolognesi M.L., Chiarini A., Minarini A., Spampinato S., Synthesis and biological activity of some methoctramine-related tetraamines bearing A 11-Acetyl-5,11-Dihydro-6h-Pyrido[2,3-B][1,4]-Benzodiazepin-6-One moiety as antimuscarinics: a second generation of highly selective M2 muscarinic receptor antagonists. (unibo.it)
  • Few highly selective M2 agonists are available at present, although there are several non-selective muscarinic agonists that stimulate M2, and a number of selective M2 antagonists are available. (wikipedia.org)
  • The orthosteric incomplete agonists arecoline (30 μM) and pilocarpine (35 μM) also induced significant M1 mACh receptor internalization (Fig. 1A). (bioshockinfinitereleasedate.com)
  • We analyzed the binding characteristics of muscarinic agonists to cardiac maCh-R by computer-assisted least square method. (nii.ac.jp)
  • We called them M2 with higher affinity for the agonists and M2 with the lower affinity. (nii.ac.jp)
  • Selectivity is important on both counts: Non-specific muscarinic receptor agonists can produce side effects due to peripheral cholinergic effects including gastrointestinal disturbances, changes in blood pressure, and excessive sweating. (alzforum.org)
  • The bladder neck contains a high concentration of receptors that are sensitive to alpha-agonists. (medscape.com)
  • Model of M2 receptor from side- (left) and extracellular- (right) view shows 7 blue α helices spanning the membrane, bound antagonists quinuclidinyl bezilate (green) and amino acids contributing to major intramolecular interactions. (cas.cz)
  • Furthermore, all ACh-induced cellular and network changes were blocked by muscarinic, but not nicotinic receptor antagonists. (springer.com)
  • A fresh class of subtype-selective muscarinic acetylcholine (mACh) receptor agonist that activates the receptor through interaction at a site distinct from the orthosteric acetylcholine binding site has been reported recently. (bioshockinfinitereleasedate.com)
  • Outcomes Perseverance of Agonist Binding Affinities in M1 M3 and M2 mACh Receptors. (bioshockinfinitereleasedate.com)
  • They show that treating cultured mouse neurons expressing human APP with the acetylcholine receptor agonist carbachol increased the production of α-secretase cleavage products, but no such effect occurred in cells from M1 knockout mice. (alzforum.org)
  • The BU72-stabilized changes in the μOR binding pocket are subtle and differ from those observed for agonist-bound structures of the β 2 -adrenergic receptor (β 2 AR) and the M2 muscarinic receptor. (bath.ac.uk)
  • In this study muscarinic receptor expression, namely M2 and M3 subtypes of muscarinic receptors were analyzed on bladder tumor samples. (auanet.org)
  • Although it has been suggested by many investigators that subtypes of muscarinic cholinergic receptors exist, physical studies of solubilized receptors have indicated that only a single molecular species may exist. (aspetjournals.org)
  • At high concentrations, alcuronium inhibits the binding of muscarinic ligands, presumably by competition for the classical muscarinic binding site. (aspetjournals.org)
  • Developing computational methods to relate receptors by the similarity of their ligands, rather than by protein sequence or structure. (ucsf.edu)
  • Since the new relationships are articulated by ligands, they may be directly tested both on isolated receptors and, increasingly, against model whole organisms, such as zebra fish, C. elegans and mice. (ucsf.edu)
  • Positive cooperativity induced by alcuronium appears to be specific for the m2 (cardiac) subtype of muscarinic receptors. (aspetjournals.org)
  • That is M1 subtype, a neuronal maCh-R, M2, a cardiac maCh-R and M3, maCh-R in other peripheral tissues. (nii.ac.jp)
  • Cardiac maCh-R (M2 subtype) are thought to consist of a single species of receptor protein. (nii.ac.jp)
  • Cardiac tissue are reported to contain only M2 mRMA. (nii.ac.jp)
  • Publications] X.M. Zhou: 'The SH-H subgroup of cardiac M_2 receptors (M_2 ) inhibits adenulate cyclase activity. (nii.ac.jp)
  • Publications] A. Mizushima: 'The H-L subgroup of guinea-pig cardiac M_2 receptors (M_2 ) regulates formation of inositol phosphates. (nii.ac.jp)
  • The β-1 adrenergic receptor (B1AR) increases cardiac output and secretion of rennin and ghrelin. (proteopedia.org)
  • These two branches control heart rate by stimulating different G protein-coupled receptors (GPCRs), which in turn activate ion channels that modify the electrical properties of cardiac pacemaker cells ( DiFrancesco, 1993 ). (elifesciences.org)
  • M2 muscarinic receptors act via a Gi type receptor, which causes a decrease in cAMP in the cell, generally leading to inhibitory-type effects. (wikipedia.org)
  • In the control group, pilocarpine (1-100 micrograms/kg iv) attenuated vagally induced bronchoconstriction by stimulating inhibitory M2-muscarinic receptors on parasympathetic nerves in the lungs. (nih.gov)
  • Release of acetylcholine is controlled by inhibitory M2 muscarinic receptors, and it appears that it is these M2 receptors that are dysfunctional in animal models of hyperresponsiveness. (nih.gov)
  • In conclusion, loss of function of inhibitory M2 muscarinic receptors on the airway parasympathetic nerves causes vagally mediated bronchoconstriction and hyperresponsiveness following antigen challenge. (nih.gov)
  • Treatment relies heavily on the use of high doses of atropine to block muscarinic receptor overactivation by acetylcholine (ACh) build up due to OP-induced block of acetylcholinesterase (AChE). (nih.gov)
  • Antimuscarinic agents , the "mainstay of treatment" for patients with OAB, block muscarinic (M2 and M3) receptors in the bladder detrusor muscle, thereby reducing frequency and urgency. (empr.com)
  • Although rarely taken into account, the non-selective inhibition of all muscarinic receptor (mAChR) subtypes by atropine may be an important determinant of these poor outcomes. (nih.gov)
  • Specifically, inhibition of presynaptic mAChRs (mostly M2), which are part of a negative feedback loop that limits ACh release from cholinergic neurons, can exacerbate the OP-induced cholinergic crisis. (nih.gov)
  • M2 couples with inhibition of adenylate cyclase and M2 with activation of PI turnover. (nii.ac.jp)
  • Activation of the M2 receptors, which are coupled to Gi, inhibits the β-adrenergic mediated relaxation of the airway smooth muscle. (wikipedia.org)
  • Synergistically, activation of the M3 receptors, which couple to Gq, stimulates contraction of the airway smooth muscle. (wikipedia.org)
  • Contraction of airway smooth muscle is mediated by M3 muscarinic receptors on the airway smooth muscle. (nih.gov)
  • The effect of antigen challenge on the function of neuronal M2-muscarinic autoreceptors in the lungs was studied in anesthetized guinea pigs. (nih.gov)
  • We have studied if Pm affects nicotinic acetylcholine receptors (nAChRs), since they play broad functional roles, both in the nervous system and non-neuronal tissues. (mdpi.com)
  • Thus, ACh modulates network dynamics in a biphasic fashion, probably by inhibiting excitatory synaptic transmission and facilitating neuronal excitability through muscarinic signaling pathways. (springer.com)
  • In neuronal cells, mainly on synaptic terminals, stimulation of the M2 autoreceptors is responsible for presynaptic muscarinic autoinhibition of acetylcholine release in both central and peripheral cholinergic neurons. (multispaninc.com)
  • Eglen (2006) Muscarinic receptor subtypes in neuronal and non-neuronal cholinergic function. (multispaninc.com)
  • One of these, muscarinic acetyl choline receptors, are expressed on both urothelial cells and detrusor muscle and play a great role in human bladder physiology. (auanet.org)
  • Specifically M2 and M3 type receptors are the most common receptors of bladder. (auanet.org)
  • M2 receptors are specially found on umbrella cells on the mucosa layer of bladder and almost up to three times more frequent than M3 receptors. (auanet.org)
  • In order to have a strong evidence of M2 and M3 subtypes in bladder tumors, the samples were analyzed both with Western blot technique and with immunohistochemistry. (auanet.org)
  • Progression rate was found higher in patients with higher M2 muscarinic receptor levels on bladder tissue samples. (auanet.org)
  • M2 and M3 muscarinic receptors not only play a great role on bladder functions but also also may be important for bladder cancer pathophysiology though, their role in the development of blader cancer has not been defined yet. (auanet.org)
  • This current trial may indicate M2 receptors to be a potential treatment target for bladder cancer. (auanet.org)
  • We studied the role of muscarinic receptor subtype on urothelium and detrusor in rats with detrusor overactivity induced by bladder outlet obstruction (BOO). (urotoday.com)
  • Anticholinergic agents inhibit the binding of acetylcholine to the cholinergic receptor, thereby suppressing involuntary bladder contraction of any etiology. (medscape.com)
  • The level of muscarinic M3 receptor mRNA present in the bladder of CBI rats was increased by silodosin. (bvsalud.org)
  • The results suggest that the binding of low concentrations of alcuronium to muscarinic receptors in the heart, ileal smooth muscle, and cerebellum allosterically increases the affinity of muscarinic receptors towards [3H]NMS, although not [3H]QNB. (aspetjournals.org)
  • Muscarinic cholinergic receptor binding sites differentiated by their affinity for pirenzepine do not interconvert. (aspetjournals.org)
  • If interconversion of high (M1) and low (M2) affinity binding sites for PZ occurs, incubation of cerebral cortical membranes with PBCM in the presence of PZ should not alter the proportions of M1 and M2 binding sites that are unalkylated (i.e., protected). (aspetjournals.org)
  • Rovatirelin binds to the human TRH receptor with higher affinity (Ki=702nM) than taltirelin (Ki=3877nM). (bvsalud.org)
  • In this study, we tested for heterogeneity in the association between the muscarinic acetylcholine M2 receptor gene (CHRM2) and alcohol dependence, reported previously in the full sample, among the subgroups of alcohol-dependent individuals with and without comorbid drug dependence. (mssm.edu)
  • The M2 muscarinic receptors are located in the heart, where they act to slow the heart rate down to normal sinus rhythm after negative stimulatory actions of the parasympathetic nervous system, by slowing the speed of depolarization. (wikipedia.org)
  • 30-fold selectivity versus M1 and M3 , and no M2 or M4 potentiator activity. (axonmedchem.com)
  • The impact of natural receptor variants and opioid metabolites on µ-opioid receptor function. (fu-berlin.de)
  • MDMA exhibited negligible affinities (greater than 500 microM) at opioid (mu, delta and kappa), central-type benzodiazepine, and corticotropin-releasing factor receptors, and at choline uptake sites and calcium channels. (erowid.org)
  • Activation of the μ-opioid receptor (μOR) is responsible for the efficacy of the most effective analgesics. (bath.ac.uk)
  • The α-2 adrenergic receptor (A2AR) inhibits insulin or glucagons release. (proteopedia.org)
  • Parafollicular (PF) cells secrete 5-HT in response to stimulation of a G-protein-coupled Ca 2+ receptor (CaR) by increased extracellular Ca 2+ (↑[Ca 2+ ] e ). (jneurosci.org)
  • In addition, Davis and coworkers show that treating neurons from M1 knockout mice with carbachol increased Aβ production, probably via stimulation of other non-M1 muscarinic receptor subtypes. (alzforum.org)
  • Conversely, chemogenetic stimulation of Pitx2 + interneurons leads to activation of M2 receptors on motoneurons, regulation of Kv2.1 channels and greater motoneuron output due to an increase in the inter-spike afterhyperpolarization and a reduction in spike half-width. (elifesciences.org)
  • Activated eosinophils release major basic protein, which binds to M2 receptors and prevents binding of acetylcholine. (nih.gov)
  • The β-2 adrenergic receptor (B2AR) triggers many relaxation reactions. (proteopedia.org)
  • 3D structures in Adrenergic receptor . (proteopedia.org)
  • Isoprenaline, see Beta-1 Adrenergic receptor , 2y03 . (proteopedia.org)
  • The human β2 adrenergic receptor bound to a G-protein ( 3sn6 ) is featured in a scene above, and additional structures are on the Adrenergic receptor page . (proteopedia.org)
  • For G s see Beta2 adrenergic receptor-Gs protein complex updated . (proteopedia.org)
  • Four subtypes (M1-M4) in muscarinic receptors (mACh-R) were discovered by the method of gene technology. (nii.ac.jp)
  • Gene expression was assessed by qPCR for muscarinic receptor types 2 (M2) and 3 (M3), collagen type 1α1 and 3α1, and SM actin. (lu.se)
  • Protein and gene expression of M3 was decreased 3 and 7 days post-BPNI, whereas M2 was unchanged. (lu.se)
  • Detrusor overactivity induced by BOO in rat is mainly mediated by M3 muscarinic receptor in detrusor, and by M2 and M3 muscarinic receptors in urothelium. (urotoday.com)
  • It seems to need to ascertain the existence of M2 and M3 muscarinic receptors in the detrusor overactivity induced by BOO in rat. (urotoday.com)
  • There must be 5 molecules of cobra toxin (red) to block the receptor (blue) as each molecule binds with an individual alpha chain on the acetylcholine receptor. (proteopedia.org)
  • Activation of muscarinic acetylcholine receptors is known to steer APP down the non-amyloidogenic, α-secretase pathway, but it has been difficult to pin the effect on a specific receptor subtype: There are five different muscarinic receptors (M1-M5) and knowing which one is involved is critical for making selective drugs and minimizing cholinergic side effects. (alzforum.org)
  • Allergen-induced M2 receptor dysfunction is absolutely dependent upon an influx of eosinophils into the airways. (nih.gov)
  • It works as a postsynaptic neurotoxin binding to the receptor as an extracellular ligand by interacting with OH group leaving the acetylcholine channel open which releases ions used in creating an action potential. (proteopedia.org)
  • Receptor expression on cell surface measured by flow cytometry (FACS) using an anti-FLAG antibody. (multispaninc.com)
  • The rank order of affinities of MDMA at various brain receptors and uptake sites are as follows: 5-HT uptake greater than alpha 2-adrenoceptors = 5-HT2 serotonin = M-1 muscarinic = H-1 histamine greater than norepinephrine uptake = M-2 muscarinic = alpha 1-adrenoceptors = beta-adrenoceptors greater than or equal to dopamine uptake = 5-HT1 serotonin much greater than D-2 dopamine greater than D-1 dopamine. (erowid.org)
  • Dopamine receptors are a class of metabotropic G protein-coupled receptors that are important in the central nervous system. (proteopedia.org)
  • The class of transmembrane acetylcholine receptors can be divided into two main groups: the muscarinic (metabotropic) and the nicotinergic (ionotropic) receptors. (axonmedchem.com)
  • Peimine (Pm), an anti-inflammatory compound from Fritillaria , is known to inhibit some voltage-dependent ion channels and muscarinic receptors, but its interaction with ligand-gated ion channels remains unexplored. (mdpi.com)
  • 6] Discovery of the first highly M5-preferring muscarinic acetylcholine receptor ligand, an M5 positive allosteric modulator derived from a series of 5-trifluoromethoxy N-benzyl isatins. (axonmedchem.com)
  • Additionally, an extensive polar network between the ligand-binding pocket and the cytoplasmic domains appears to play a similar role in signal propagation for all three G-protein-coupled receptors. (bath.ac.uk)
  • Loss of function of these M2 receptors, as occurs in some patients with asthma and in animal models of inflammation, leads to an increase in vagally mediated hyperreactivity. (multispaninc.com)
  • Applying these to G-Protein Coupled Receptors (GPCRs), which are the single largest family of signaling receptors in human cells. (ucsf.edu)
  • Studies in developing rodents indicate that nicotine is a neuroteratogen that disrupts brain development by stimulating nicotinic acetylcholine receptors (nAChRs) that control neural cell replication and differentiation. (nature.com)
  • It is possible that M2 and M2 come from dif-ferent modification of receptor proteins, such as phosphorylation, methylation, association with other protein or polymerization. (nii.ac.jp)
  • M1, M3, M5 receptors are coupled with G q proteins, while M2 and M4 receptors are coupled with G i/o proteins. (proteopedia.org)
  • The M3 receptor-mediated K(+) current (IKM3), a G(q) protein-coupled K(+) channel. (nih.gov)
  • Comparable contrasting effects of oxo-M and AC-42 were also seen in a different CHO-M1 clone with a lower human M1 mACh receptor appearance level (~300 fmol mg?1 protein). (bioshockinfinitereleasedate.com)
  • The adrenergic receptors are metabolic G protein-coupled receptors. (proteopedia.org)
  • Stimulated muscarinic acetylcholine receptors (M2Rs) release Gβγ subunits, which slow heart rate by activating a G protein-gated K + channel (GIRK). (elifesciences.org)
  • The higher rate of Gβγ release is attributable to a faster G protein coupled receptor - G protein trimer association rate in M2R compared to β2AR. (elifesciences.org)
  • The activated receptor catalyzes removal of GDP from the G protein alpha subunit (Gα i ), which allows intracellular GTP to bind. (elifesciences.org)
  • The muscarinic acetylcholine receptor has been a target for AD therapies for decades, based first on the loss of acetylcholine in the disease and the role of M1 receptors in memory and cognition, and then on the finding that the receptors control the processing of amyloid precursor protein to Aβ peptides. (alzforum.org)
  • Unlike the nicotinergic acetylcholine receptor, the muscarinic type is part of the family of G-protein coupled receptors (GPCR-A18). (axonmedchem.com)
  • Western blots measured M2 and M3 protein expression. (lu.se)
  • The muscarinic M2 receptor is a 466-amino acid, 7-transmembrane protein. (multispaninc.com)
  • Fetal brain regions and peripheral tissues were examined for nAChR subtypes, other neurotransmitter receptors, and indices of cell signaling and cell damage. (nature.com)
  • Pseudoephedrine stimulates vasoconstriction by directly activating alpha-adrenergic receptors. (medscape.com)
  • related tetraamines bearing a 11-Acetyl-5,11-Dyhidro-6h-Pyrido[2,3-B] [1,4]-Benzodiazepin-6-One Moiety: structural requirements for optimum occupancy of muscarinic receptor subtypes as revealed by symmetrical and unsymmetrical polyamines, Journal of Medicinal Chemistry, 37, 3363-3372, 1994. (unibo.it)
  • An Open-label Positron Emission Tomography Phase I Study to Determine Muscarinic Receptor Occupancy in the Lungs in Healthy Volunteers after Inhalation of Single Dose of Tiotropium or AZD2115. (astrazenecaclinicaltrials.com)
  • Both M2 and M3 muscarinic receptors are expressed in the smooth muscles of the airway, with the majority of the receptors being the M2 type. (wikipedia.org)
  • The rates of [3H]NMS association to and dissociation from muscarinic binding sites in the atria were diminished by 10(-5) M alcuronium. (aspetjournals.org)
  • In the absence of PZ, treatment of cerebral cortical membranes with 20 nM PBCM at 4 degrees C for 50 min resulted in a 69% reduction in the density of M1 binding sites and a 55% reduction in the density of M2 binding sites with no change in the equilibrium dissociation constants of the radioligands [3H]quinuclidinyl benzilate or [3H]PZ. (aspetjournals.org)