Alpha7 nicotinic acetylcholine receptor. Medical search

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.

A member of the NICOTINIC ACETYLCHOLINE RECEPTOR subfamily of the LIGAND-GATED ION CHANNEL family. It consists entirely of pentameric a7 subunits expressed in the CNS, autonomic nervous system, vascular system, lymphocytes and spleen.

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.

Drugs that bind to and activate nicotinic cholinergic receptors (RECEPTORS, NICOTINIC). Nicotinic agonists act at postganglionic nicotinic receptors, at neuroeffector junctions in the peripheral nervous system, and at nicotinic receptors in the central nervous system. Agents that function as neuromuscular depolarizing blocking agents are included here because they activate nicotinic receptors, although they are used clinically to block nicotinic transmission.

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.

A genus of the Torpedinidae family consisting of several species. Members of this family have powerful electric organs and are commonly called electric rays.

Neurotoxic proteins from the venom of the banded or Formosan krait (Bungarus multicinctus, an elapid snake). alpha-Bungarotoxin blocks nicotinic acetylcholine receptors and has been used to isolate and study them; beta- and gamma-bungarotoxins act presynaptically causing acetylcholine release and depletion. Both alpha and beta forms have been characterized, the alpha being similar to the large, long or Type II neurotoxins from other elapid venoms.

Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.

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.

Peptide neurotoxins from the marine fish-hunting snails of the genus CONUS. They contain 13 to 29 amino acids which are strongly basic and are highly cross-linked by disulfide bonds. There are three types of conotoxins, omega-, alpha-, and mu-. OMEGA-CONOTOXINS inhibit voltage-activated entry of calcium into the presynaptic membrane and therefore the release of ACETYLCHOLINE. Alpha-conotoxins inhibit the postsynaptic acetylcholine receptor. Mu-conotoxins prevent the generation of muscle action potentials. (From Concise Encyclopedia Biochemistry and Molecular Biology, 3rd ed)

A C19 norditerpenoid alkaloid (DITERPENES) from the root of ACONITUM plants. It activates VOLTAGE-GATED SODIUM CHANNELS. It has been used to induce ARRHYTHMIAS in experimental animals and it has antiinflammatory and antineuralgic properties.

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.

Dihydro analog of beta-erythroidine, which is isolated from the seeds and other plant parts of Erythrina sp. Leguminosae. It is an alkaloid with curarimimetic properties.

A class of saturated compounds consisting of two rings only, having two or more atoms in common, containing at least one hetero atom, and that take the name of an open chain hydrocarbon containing the same total number of atoms. (From Riguady et al., Nomenclature of Organic Chemistry, 1979, p31)

In about 250 species of electric fishes, modified muscle fibers forming disklike multinucleate plates arranged in stacks like batteries in series and embedded in a gelatinous matrix. A large torpedo ray may have half a million plates. Muscles in different parts of the body may be modified, i.e., the trunk and tail in the electric eel, the hyobranchial apparatus in the electric ray, and extrinsic eye muscles in the stargazers. Powerful electric organs emit pulses in brief bursts several times a second. They serve to stun prey and ward off predators. A large torpedo ray can produce of shock of more than 200 volts, capable of stunning a human. (Storer et al., General Zoology, 6th ed, p672)

Toxins, contained in cobra (Naja) venom that block cholinergic receptors; two specific proteins have been described, the small (short, Type I) and the large (long, Type II) which also exist in other Elapid venoms.

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 neuromuscular blocker and active ingredient in CURARE; plant based alkaloid of Menispermaceae.

The commonest and widest ranging species of the clawed "frog" (Xenopus) in Africa. This species is used extensively in research. There is now a significant population in California derived from escaped laboratory animals.

Single chains of amino acids that are the units of multimeric PROTEINS. Multimeric proteins can be composed of identical or non-identical subunits. One or more monomeric subunits may compose a protomer which itself is a subunit structure of a larger assembly.

Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.

A disorder of neuromuscular transmission characterized by weakness of cranial and skeletal muscles. Autoantibodies directed against acetylcholine receptors damage the motor endplate portion of the NEUROMUSCULAR JUNCTION, impairing the transmission of impulses to skeletal muscles. Clinical manifestations may include diplopia, ptosis, and weakness of facial, bulbar, respiratory, and proximal limb muscles. The disease may remain limited to the ocular muscles. THYMOMA is commonly associated with this condition. (Adams et al., Principles of Neurology, 6th ed, p1459)

A selective nicotinic cholinergic agonist used as a research tool. DMPP activates nicotinic receptors in autonomic ganglia but has little effect at the neuromuscular junction.

A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS.

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.

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).

Venoms produced by frogs, toads, salamanders, etc. The venom glands are usually on the skin of the back and contain cardiotoxic glycosides, cholinolytics, and a number of other bioactive materials, many of which have been characterized. The venoms have been used as arrow poisons and include bufogenin, bufotoxin, bufagin, bufotalin, histrionicotoxins, and pumiliotoxin.

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.

The synapse between a neuron and a muscle.

A piperidine botanical insecticide.

Contractile tissue that produces movement in animals.

The relationship between the dose of an administered drug and the response of the organism to the drug.

Compounds containing the PhCH= radical.

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.

Agents that mimic neural transmission by stimulation of the nicotinic receptors on postganglionic autonomic neurons. Drugs that indirectly augment ganglionic transmission by increasing the release or slowing the breakdown of acetylcholine or by non-nicotinic effects on postganglionic neurons are not included here nor are the nonspecific cholinergic agonists.

Drugs that bind to and activate cholinergic receptors.

Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.

A benzazepine derived from norbelladine. It is found in GALANTHUS and other AMARYLLIDACEAE. It is a cholinesterase inhibitor that has been used to reverse the muscular effects of GALLAMINE TRIETHIODIDE and TUBOCURARINE and has been studied as a treatment for ALZHEIMER DISEASE and other central nervous system disorders.

The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.

The parts of a macromolecule that directly participate in its specific combination with another molecule.

Organic nitrogenous bases. Many alkaloids of medical importance occur in the animal and vegetable kingdoms, and some have been synthesized. (Grant & Hackh's Chemical Dictionary, 5th ed)

Unsaturated azacyclopropane compounds that are three-membered heterocycles of a nitrogen and two carbon atoms.

A protein component of the synaptic basal lamina. It has been shown to induce clustering of acetylcholine receptors on the surface of muscle fibers and other synaptic molecules in both synapse regeneration and development.

Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.

An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.

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.

Drugs that bind to but do not activate CHOLINERGIC RECEPTORS, thereby blocking the actions of ACETYLCHOLINE or cholinergic agonists.

Vesicular amine transporter proteins that transport the neurotransmitter ACETYLCHOLINE into small SECRETORY VESICLES. Proteins of this family contain 12 transmembrane domains and exchange vesicular PROTONS for cytoplasmic acetylcholine.

A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism.

Venoms from mollusks, including CONUS and OCTOPUS species. The venoms contain proteins, enzymes, choline derivatives, slow-reacting substances, and several characterized polypeptide toxins that affect the nervous system. Mollusk venoms include cephalotoxin, venerupin, maculotoxin, surugatoxin, conotoxins, and murexine.

Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).

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.

Drug agonism involving selective binding but reduced effect. This can result in some degree of DRUG ANTAGONISM.

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.

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.

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 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).

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.

A genus of cone-shaped marine snails in the family Conidae, class GASTROPODA. It comprises more than 600 species, many containing unique venoms (CONUS VENOMS) with which they immobilize their prey.

Tobacco used to the detriment of a person's health or social functioning. Tobacco dependence is included.

Biologically active molecules which are covalently bound to the enzymes or binding proteins normally acting on them. Binding occurs due to activation of the label by ultraviolet light. These labels are used primarily to identify binding sites on proteins.

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.

The rate dynamics in chemical or physical systems.

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.

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.

The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability.

The specialized postsynaptic region of a muscle cell. The motor endplate is immediately across the synaptic cleft from the presynaptic axon terminal. Among its anatomical specializations are junctional folds which harbor a high density of cholinergic receptors.

An inhibitor of drug metabolism and CYTOCHROME P-450 ENZYME SYSTEM activity.

The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.

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.

Compounds having the nitro group, -NO2, attached to carbon. When attached to nitrogen they are nitramines and attached to oxygen they are NITRATES.

Compounds with BENZENE fused to AZEPINES.

Chemically stimulated aggregation of cell surface receptors, which potentiates the action of the effector cell.

A subclass of serotonin receptors that form cation channels and mediate signal transduction by depolarizing the cell membrane. The cation channels are formed from 5 receptor subunits. When stimulated the receptors allow the selective passage of SODIUM; POTASSIUM; and CALCIUM.

Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.

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.

Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.

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 modification of the reactivity of ENZYMES by the binding of effectors to sites (ALLOSTERIC SITES) on the enzymes other than the substrate BINDING SITES.

A heterogeneous group of disorders characterized by a congenital defect in neuromuscular transmission at the NEUROMUSCULAR JUNCTION. This includes presynaptic, synaptic, and postsynaptic disorders (that are not of autoimmune origin). The majority of these diseases are caused by mutations of various subunits of the nicotinic acetylcholine receptor (RECEPTORS, NICOTINIC) on the postsynaptic surface of the junction. (From Arch Neurol 1999 Feb;56(2):163-7)

The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.

Established cell cultures that have the potential to propagate indefinitely.

A subclass of muscarinic receptor that mediates cholinergic-induced contraction in a variety of SMOOTH MUSCLES.

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.

Azoles with an OXYGEN and a NITROGEN next to each other at the 1,2 positions, in contrast to OXAZOLES that have nitrogens at the 1,3 positions.

Cell membranes associated with synapses. Both presynaptic and postsynaptic membranes are included along with their integral or tightly associated specializations for the release or reception of transmitters.

The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.

The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.

A genus of fish, in the family GYMNOTIFORMES, capable of producing an electric shock that immobilizes fish and other prey. The species Electrophorus electricus is also known as the electric eel, though it is not a true eel.

Toxins isolated from the venom of Laticauda semifasciata, a sea snake (Hydrophid); immunogenic, basic polypeptides of 62 amino acids, folded by four disulfide bonds, block neuromuscular end-plates irreversibly, thus causing paralysis and severe muscle damage; they are similar to Elapid neurotoxins.

Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept.

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.

Compounds that contain the decamethylenebis(trimethyl)ammonium radical. These compounds frequently act as neuromuscular depolarizing agents.

An alkaloid that has actions similar to NICOTINE on nicotinic cholinergic receptors but is less potent. It has been proposed for a variety of therapeutic uses including in respiratory disorders, peripheral vascular disorders, insomnia, and smoking cessation.

Bicyclic bridged compounds that contain a nitrogen which has three bonds. The nomenclature indicates the number of atoms in each path around the rings, such as [2.2.2] for three equal length paths. Some members are TROPANES and BETA LACTAMS.

Venoms from snakes of the genus Naja (family Elapidae). They contain many specific proteins that have cytotoxic, hemolytic, neurotoxic, and other properties. Like other elapid venoms, they are rich in enzymes. They include cobramines and cobralysins.

Drugs used to specifically facilitate learning or memory, particularly to prevent the cognitive deficits associated with dementias. These drugs act by a variety of mechanisms. While no potent nootropic drugs have yet been accepted for general use, several are being actively investigated.

The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).

An alkaloid, originally from Atropa belladonna, but found in other plants, mainly SOLANACEAE. Hyoscyamine is the 3(S)-endo isomer of atropine.

A hallucinogen formerly used as a veterinary anesthetic, and briefly as a general anesthetic for humans. Phencyclidine is similar to KETAMINE in structure and in many of its effects. Like ketamine, it can produce a dissociative state. It exerts its pharmacological action through inhibition of NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE). As a drug of abuse, it is known as PCP and Angel Dust.

The resection or removal of the innervation of a muscle or muscle tissue.

Derivatives of ammonium compounds, NH4+ Y-, in which all four of the hydrogens bonded to nitrogen have been replaced with hydrocarbyl groups. These are distinguished from IMINES which are RN=CR2.

A high-affinity muscarinic antagonist commonly used as a tool in animal and tissue studies.

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.

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.

A family of extremely venomous snakes, comprising coral snakes, cobras, mambas, kraits, and sea snakes. They are widely distributed, being found in the southern United States, South America, Africa, southern Asia, Australia, and the Pacific Islands. The elapids include three subfamilies: Elapinae, Hydrophiinae, and Lauticaudinae. Like the viperids, they have venom fangs in the front part of the upper jaw. The mambas of Africa are the most dangerous of all snakes by virtue of their size, speed, and highly toxic venom. (Goin, Goin, and Zug, Introduction to Herpetology, 3d ed, p329-33)

A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.

A small protuberance at the dorsal, posterior corner of the wall of the THIRD VENTRICLE, adjacent to the dorsal THALAMUS and PINEAL BODY. It contains the habenular nuclei and is a major part of the epithalamus.

A localization-related (focal) form of epilepsy characterized by seizures which arise in the FRONTAL LOBE. A variety of clinical syndromes exist depending on the exact location of the seizure focus. Frontal lobe seizures may be idiopathic (cryptogenic) or caused by an identifiable disease process such as traumatic injuries, neoplasms, or other macroscopic or microscopic lesions of the frontal lobes (symptomatic frontal lobe seizures). (From Adams et al., Principles of Neurology, 6th ed, pp318-9)

Antinematodal agent used mainly for livestock.

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.

A genus of dextrally coiled freshwater snails that includes some species of importance as intermediate hosts of parasitic flukes.

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.

One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.

Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates.

Common name for the species Gallus gallus, the domestic fowl, in the family Phasianidae, order GALLIFORMES. It is descended from the red jungle fowl of SOUTHEAST ASIA.

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.

The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.

Solutions or mixtures of toxic and nontoxic substances elaborated by snake (Ophidia) salivary glands for the purpose of killing prey or disabling predators and delivered by grooved or hollow fangs. They usually contain enzymes, toxins, and other factors.

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)

Plant extracts from several species, including genera STRYCHNOS and Chondodendron, which contain TETRAHYDROISOQUINOLINES that produce PARALYSIS of skeletal muscle. These extracts are toxic and must be used with the administration of artificial respiration.

Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes.

A muscarinic antagonist used to study binding characteristics of muscarinic cholinergic receptors.

Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions.

The instinctive tendency (or ability) to assume a normal position of the body in space when it has been displaced.

An antihelminthic drug that has been tried experimentally in rheumatic disorders where it apparently restores the immune response by increasing macrophage chemotaxis and T-lymphocyte function. Paradoxically, this immune enhancement appears to be beneficial in rheumatoid arthritis where dermatitis, leukopenia, and thrombocytopenia, and nausea and vomiting have been reported as side effects. (From Smith and Reynard, Textbook of Pharmacology, 1991, p435-6)

The developmental entity of a fertilized chicken egg (ZYGOTE). The developmental process begins about 24 h before the egg is laid at the BLASTODISC, a small whitish spot on the surface of the EGG YOLK. After 21 days of incubation, the embryo is fully developed before hatching.

The largest and uppermost of the paravertebral sympathetic ganglia.

Agents that inhibit the actions of the parasympathetic nervous system. The major group of drugs used therapeutically for this purpose is the MUSCARINIC ANTAGONISTS.

Elements of limited time intervals, contributing to particular results or situations.

Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.

Any autoimmune animal disease model used in the study of MYASTHENIA GRAVIS. Injection with purified neuromuscular junction acetylcholine receptor (AChR) (see RECEPTORS, CHOLINERGIC) components results in a myasthenic syndrome that has acute and chronic phases. The motor endplate pathology, loss of acetylcholine receptors, presence of circulating anti-AChR antibodies, and electrophysiologic changes make this condition virtually identical to human myasthenia gravis. Passive transfer of AChR antibodies or lymphocytes from afflicted animals to normals induces passive transfer experimental autoimmune myasthenia gravis. (From Joynt, Clinical Neurology, 1997, Ch 54, p3)

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.

The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.

An enzyme that catalyzes the formation of acetylcholine from acetyl-CoA and choline. EC 2.3.1.6.

Use of electric potential or currents to elicit biological responses.

Proteins prepared by recombinant DNA technology.

Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.

A region in the MESENCEPHALON which is dorsomedial to the SUBSTANTIA NIGRA and ventral to the RED NUCLEUS. The mesocortical and mesolimbic dopaminergic systems originate here, including an important projection to the NUCLEUS ACCUMBENS. Overactivity of the cells in this area has been suspected to contribute to the positive symptoms of SCHIZOPHRENIA.

The family of agile, keen-sighted mongooses of Asia and Africa that feed on RODENTS and SNAKES.

A nicotinic antagonist used primarily as a ganglionic blocker in animal research. It has been used as an antihypertensive agent but has been supplanted by more specific drugs in most clinical applications.

Cells that store epinephrine secretory vesicles. During times of stress, the nervous system signals the vesicles to secrete their hormonal content. Their name derives from their ability to stain a brownish color with chromic salts. Characteristically, they are located in the adrenal medulla and paraganglia (PARAGANGLIA, CHROMAFFIN) of the sympathetic nervous system.

The functions and activities of living organisms or their parts involved in generating and responding to electrical charges .

The most common inhibitory neurotransmitter in the central nervous system.

Stable iodine atoms that have the same atomic number as the element iodine, but differ in atomic weight. I-127 is the only naturally occurring stable iodine isotope.

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 subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles.

Physiological and psychological symptoms associated with withdrawal from the use of a drug after prolonged administration or habituation. The concept includes withdrawal from smoking or drinking, as well as withdrawal from an administered drug.

Unstable isotopes of rubidium that decay or disintegrate emitting radiation. Rb atoms with atomic weights 79-84, and 86-95 are radioactive rubidium isotopes.

Compounds containing the hexamethylenebis(trimethylammonium) cation. Members of this group frequently act as antihypertensive agents and selective ganglionic blocking agents.

A non-hydrolyzed muscarinic agonist used as a research tool.

Limbless REPTILES of the suborder Serpentes.

A depolarizing neuromuscular-blocking agent, that causes persistent nicotinic activation resulting in spastic paralysis of susceptible nematodes. It is a drug of second-choice after benzimidazoles for treatment of ascariasis, hookworm, and pinworm infections, being effective after a single dose. (From Smith and Reynard, Textbook of Pharmacology, 1992, p920)

Nerve fibers liberating acetylcholine at the synapse after an impulse.

Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.

Refers to animals in the period of time just after birth.

RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.

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.

Compounds that include the amino-N-phenylamide structure.

The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.

Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.

A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.

The observable response an animal makes to any situation.

The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)

The action of a drug that may affect the activity, metabolism, or toxicity of another drug.

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.

Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE.

Most generally any NEURONS which are not motor or sensory. Interneurons may also refer to neurons whose AXONS remain within a particular brain region in contrast to projection neurons, which have axons projecting to other brain regions.

Drugs that interrupt transmission of nerve impulses at the skeletal neuromuscular junction. They can be of two types, competitive, stabilizing blockers (NEUROMUSCULAR NONDEPOLARIZING AGENTS) or noncompetitive, depolarizing agents (NEUROMUSCULAR DEPOLARIZING AGENTS). Both prevent acetylcholine from triggering the muscle contraction and they are used as anesthesia adjuvants, as relaxants during electroshock, in convulsive states, etc.

An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order TETRAODONTIFORMES, which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction.

The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.

The dorsal portion or roof of the midbrain which is composed of two pairs of bumps, the INFERIOR COLLICULI and the SUPERIOR COLLICULI. These four colliculi are also called the quadrigeminal bodies (TECTUM MESENCEPHALI). They are centers for visual sensorimotor integration.

A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment.

The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.

A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation.

Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.

Analogs of those substrates or compounds which bind naturally at the active sites of proteins, enzymes, antibodies, steroids, or physiological receptors. These analogs form a stable covalent bond at the binding site, thereby acting as inhibitors of the proteins or steroids.

Substances used for their pharmacological actions on any aspect of neurotransmitter systems. Neurotransmitter agents include agonists, antagonists, degradation inhibitors, uptake inhibitors, depleters, precursors, and modulators of receptor function.

The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.

N-methyl-8-azabicyclo[3.2.1]octanes best known for the ones found in PLANTS.

The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included.

The making of a radiograph of an object or tissue by recording on a photographic plate the radiation emitted by radioactive material within the object. (Dorland, 27th ed)

Clusters of neurons and their processes in the autonomic nervous system. In the autonomic ganglia, the preganglionic fibers from the central nervous system synapse onto the neurons whose axons are the postganglionic fibers innervating target organs. The ganglia also contain intrinsic neurons and supporting cells and preganglionic fibers passing through to other ganglia.

Plasma glycoprotein member of the serpin superfamily which inhibits TRYPSIN; NEUTROPHIL ELASTASE; and other PROTEOLYTIC ENZYMES.

The ability of a substrate to allow the passage of ELECTRONS.

Imidazole derivative anesthetic and hypnotic with little effect on blood gases, ventilation, or the cardiovascular system. It has been proposed as an induction anesthetic.

The study of the chemical and physical phenomena of radioactive substances.

Disorders of the AUTONOMIC NERVOUS SYSTEM occurring as a primary condition. Manifestations can involve any or all body systems but commonly affect the BLOOD PRESSURE and HEART RATE.

The protein constituents of muscle, the major ones being ACTINS and MYOSINS. More than a dozen accessory proteins exist including TROPONIN; TROPOMYOSIN; and DYSTROPHIN.

Marine, freshwater, or terrestrial mollusks of the class Gastropoda. Most have an enclosing spiral shell, and several genera harbor parasites pathogenic to man.

Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics.

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.

Drugs that interrupt transmission at the skeletal neuromuscular junction without causing depolarization of the motor end plate. They prevent acetylcholine from triggering muscle contraction and are used as muscle relaxants during electroshock treatments, in convulsive states, and as anesthesia adjuvants.

Selective effects of a 4-oxystilbene derivative on wild and mutant neuronal chick alpha7 nicotinic receptor. (1/725)

1. We assessed the pharmacological activity of triethyl-(beta-4-stilbenoxy-ethyl) ammonium (MG624), a drug that is active on neuronal nicotinic receptors (nicotinic AChR). Experiments on the major nicotinic AChR subtypes present in chick brain, showed that it inhibits the binding of [125I]-alphaBungarotoxin (alphaBgtx) to the alpha7 subtype, and that of [3H]-epibatidine (Epi) to the alpha4beta2 subtype, with Ki values of respectively 106 nM and 84 microM. 2. MG624 also inhibited ACh elicited currents (I(ACh)) in the oocyte-expressed alpha7 and alpha4beta2 chick subtypes with half-inhibitory concentrations (IC50) of respectively 109 nM and 3.2 microM. 3. When tested on muscle-type AChR, it inhibited [125I]-alphaBgtx binding with a Ki of 32 microM and ACh elicited currents (I(ACh)) in the oocyte-expressed alpha1beta1gammadelta chick subtype with an IC50 of 2.9 microM. 4. The interaction of MG624 with the alpha7 subtype was investigated using an alpha7 homomeric mutant receptor with a threonine-for-leucine 247 substitution (L247T alpha7). MG624 did not induce any current in oocytes expressing the wild type alpha7 receptor, but did induce large currents in the oocyte-expressed L247T alpha7 receptor. The MG624 elicited current (I(MG62)) has an EC50 of 0.2 nM and a Hill coefficient nH of 1.9, and is blocked by the nicotinic receptor antagonist methyllycaconitine (MLA). 5. These binding and electrophysiological studies show that MG624 is a potent antagonist of neuronal chick alpha7 nicotinic AChR, and becomes a competitive agonist following the mutation of the highly conserved leucine residue 247 located in the M2 channel domain. (+info)

Pairwise interactions between neuronal alpha7 acetylcholine receptors and alpha-conotoxin ImI. (2/725)

The present work uses alpha-conotoxin ImI (CTx ImI) to probe the neurotransmitter binding site of neuronal alpha7 acetylcholine receptors. We identify key residues in alpha7 that contribute to CTx ImI affinity, and use mutant cycles analysis to identify pairs of residues that stabilize the receptor-conotoxin complex. We first mutated key residues in the seven known loops of alpha7 that converge at the subunit interface to form the ligand binding site. The mutant subunits were expressed in 293 HEK cells, and CTx ImI binding was measured by competition against the initial rate of 125I-alpha-bungarotoxin binding. The results reveal a predominant contribution by Tyr-195 in alpha7, accompanied by smaller contributions by Thr-77, Tyr-93, Asn-111, Gln-117, and Trp-149. Based upon our previous identification of bioactive residues in CTx ImI, we measured binding of receptor and toxin mutations and analyzed the results using thermodynamic mutant cycles. The results reveal a single dominant interaction between Arg-7 of CTx ImI and Tyr-195 of alpha7 that anchors the toxin to the binding site. We also find multiple weak interactions between Asp-5 of CTx ImI and Trp-149, Tyr-151, and Gly-153 of alpha7, and between Trp-10 of CTx ImI and Thr-77 and Asn-111 of alpha7. The overall results establish the orientation of CTx ImI as it bridges the subunit interface and demonstrate close approach of residues on opposing faces of the alpha7 binding site. (+info)

alpha-bungarotoxin receptors contain alpha7 subunits in two different disulfide-bonded conformations. (3/725)

Neuronal nicotinic alpha7 subunits assemble into cell-surface complexes that neither function nor bind alpha-bungarotoxin when expressed in tsA201 cells. Functional alpha-bungarotoxin receptors are expressed if the membrane-spanning and cytoplasmic domains of the alpha7 subunit are replaced by the homologous regions of the serotonin-3 receptor subunit. Bgt-binding surface receptors assembled from chimeric alpha7/serotonin-3 subunits contain subunits in two different conformations as shown by differences in redox state and other features of the subunits. In contrast, alpha7 subunit complexes in the same cell line contain subunits in a single conformation. The appearance of a second alpha7/serotonin-3 subunit conformation coincides with the formation of alpha-bungarotoxin-binding sites and intrasubunit disulfide bonding, apparently within the alpha7 domain of the alpha7/serotonin-3 chimera. In cell lines of neuronal origin that produce functional alpha7 receptors, alpha7 subunits undergo a conformational change similar to alpha7/serotonin-3 subunits. alpha7 subunits, thus, can fold and assemble by two different pathways. Subunits in a single conformation assemble into nonfunctional receptors, or subunits expressed in specialized cells undergo additional processing to produce functional, alpha-bungarotoxin-binding receptors with two alpha7 conformations. Our results suggest that alpha7 subunit diversity can be achieved postranslationally and is required for functional homomeric receptors. (+info)

Minimal conformation of the alpha-conotoxin ImI for the alpha7 neuronal nicotinic acetylcholine receptor recognition: correlated CD, NMR and binding studies. (4/725)

The alpha-ImI conotoxin, a selective potent inhibitor of the mammalian neuronal alpha7 nicotinic acetylcholine receptor (n-AchR), was shown by point mutation or by L-alanine scanning to display two regions essential for bioactivity: the active site Asp5-Pro6-Arg7 in the first loop and Trp10 in the second loop. The deletion of the Cys3,Cys12 disulfide bond in the alpha-ImI scaffold, e.g. peptide II, had no effect on its binding affinity. CD spectra, NMR studies and structure calculations were carried out on the wild type alpha-ImI, the weakest analog (R7A) and peptide II (equipotent to alpha-ImI) in order to point out the conformational differences between these compounds. Then, an attempt to correlate the conformational data and the affinity results was proposed. CD and NMR data were identical for the R7A analog and alpha-ImI, revealing the crucial functional role of the Arg7 side chain. On the other hand, the scaffold of the first loop in peptide II was shown by NMR to represent the minimal conformation for the optimal interaction of the toxin with the neuronal alpha7 n-AchR. Last, the beta-turn forming property of the 6th residue (Pro) in the active site of the alpha-ImI can be correlated with its affinity. (+info)

Alpha7 nicotinic receptor subunits are not necessary for hippocampal-dependent learning or sensorimotor gating: a behavioral characterization of Acra7-deficient mice. (5/725)

The alpha7 nicotinic acetylcholine receptor (nAChR) subunit is abundantly expressed in the hippocampus and contributes to hippocampal cholinergic synaptic transmission suggesting that it may contribute to learning and memory. There is also evidence for an association between levels of alpha7 nAChR and in sensorimotor gating impairments. To examine the role of alpha7 nAChRs in learning and memory and sensorimotor gating, Acra7 homozygous mutant mice and their wild-type littermates were tested in a Pavlovian conditioned fear test, for spatial learning in the Morris water task, and in the prepulse inhibition paradigm. Exploratory activity, motor coordination, and startle habituation were also evaluated. Acra7 mutant mice displayed the same levels of contextual and auditory-cue condition fear as wild-type mice. Similarly, there were no differences in spatial learning performance between mutant and wild-type mice. Finally, Acra7 mutant and wild-type mice displayed similar levels of prepulse inhibition. Other behavioral responses in Acra7 mutant mice were also normal, except for an anxiety-related behavior in the open-field test. The results of this study show that the absence of alpha7 nAChRs has little impact on normal, base-line behavioral responses. Future studies will examine the contribution of alpha7 nAChR to the enhancement of learning and sensorimotor gating following nicotine treatments. (+info)

Cell-free expression and functional reconstitution of homo-oligomeric alpha7 nicotinic acetylcholine receptors into planar lipid bilayers. (6/725)

The alpha7 nicotinic acetylcholine receptor (nAChR) is a ligand-gated ion channel that modulates neurotransmitter release in the central nervous system. We show here that functional, homo-oligomeric alpha7 nAChRs can be synthesized in vitro with a rabbit reticulocyte lysate translation system supplemented with endoplasmic reticulum microsomes, reconstituted into planar lipid bilayers, and evaluated using single-channel recording techniques. Because wild-type alpha7 nAChRs desensitize rapidly, we used a nondesensitizing form of the alpha7 receptor with mutations in the second transmembrane domain (S2'T and L9'T) to record channel activity in the continuous presence of agonist. Endoglycosidase H treatment of microsomes containing nascent alpha7 S2'T/L9'T nAChRs indicated that the receptors were glycosylated. A proteinase K protection assay revealed a 36-kDa fragment in the ER lumen, consistent with a large extracellular domain predicted by most topological models, indicating that the protein was folded integrally through the ER membrane. alpha7 S2'T/L9'T receptors reconstituted into planar lipid bilayers had a unitary conductance of approximately 50 pS, were highly selective for monovalent cations over Cl(-), were nonselective between K(+) and Na(+), and were blocked by alpha-bungarotoxin. This is the first demonstration that a functional ligand-gated ion channel can be synthesized using an in vitro expression system. (+info)

Strychnine activates neuronal alpha7 nicotinic receptors after mutations in the leucine ring and transmitter binding site domains. (7/725)

Recent work has shown that strychnine, the potent and selective antagonist of glycine receptors, is also an antagonist of nicotinic acetylcholine (AcCho) receptors including neuronal homomeric alpha7 receptors, and that mutating Leu-247 of the alpha7 nicotinic AcCho receptor-channel domain (L247Talpha7; mut1) converts some nicotinic antagonists into agonists. Therefore, a study was made of the effects of strychnine on Xenopus oocytes expressing the chick wild-type alpha7 or L247Talpha7 receptors. In these oocytes, strychnine itself did not elicit appreciable membrane currents but reduced the currents elicited by AcCho in a reversible and dose-dependent manner. In sharp contrast, in oocytes expressing L247Talpha(7) receptors with additional mutations at Cys-189 and Cys-190, in the extracellular N-terminal domain (L247T/C189-190Salpha7; mut2), micromolar concentrations of strychnine elicited inward currents that were reversibly inhibited by the nicotinic receptor blocker alpha-bungarotoxin. Single-channel recordings showed that strychnine gated mut2-channels with two conductance levels, 56 pS and 42 pS, and with kinetic properties similar to AcCho-activated channels. We conclude that strychnine is a modulator, as well as an activator, of some homomeric nicotinic alpha7 receptors. After injecting oocytes with mixtures of cDNAs encoding mut1 and mut2 subunits, the expressed hybrid receptors were activated by strychnine, similar to the mut2, and had a high affinity to AcCho like the mut1. A pentameric symmetrical model yields the striking conclusion that two identical alpha7 subunits may be sufficient to determine the functional properties of alpha7 receptors. (+info)

Nicotinic receptor activation in human cerebral cortical interneurons: a mechanism for inhibition and disinhibition of neuronal networks. (8/725)

Cholinergic control of the activity of human cerebral cortical circuits has long been thought to be accounted for by the interaction of acetylcholine (ACh) with muscarinic receptors. Here we report the discovery of functional nicotinic receptors (nAChRs) in interneurons of the human cerebral cortex and discuss the physiological and clinical implications of these findings. The whole-cell mode of the patch-clamp technique was used to record responses triggered by U-tube application of the nonselective agonist ACh and of the alpha7-nAChR-selective agonist choline to interneurons visualized by means of infrared-assisted videomicroscopy in slices of the human cerebral cortex. Choline induced rapidly desensitizing whole-cell currents that, being sensitive to blockade by methyllycaconitine (MLA; 50 nM), were most likely subserved by an alpha7-like nAChR. In contrast, ACh evoked slowly decaying whole-cell currents that, being sensitive to blockade by dihydro-beta-erythroidine (DHbetaE; 10 microM), were most likely subserved by an alpha4beta2-like nAChR. Application of ACh (but not choline) to the slices also triggered GABAergic postsynaptic currents (PSCs). Evidence is provided that ACh-evoked PSCs are the result of activation of alpha4beta2-like nAChRs present in preterminal axon segments and/or in presynaptic terminals of interneurons. Thus, nAChRs can relay inhibitory and/or disinhibitory signals to pyramidal neurons and thereby modulate the activity of neuronal circuits in the human cerebral cortex. These mechanisms, which appear to be retained across species, can account for the involvement of nAChRs in cognitive functions and in certain neuropathological conditions. (+info)

The symptoms of myasthenia gravis can vary in severity and may include:

* Weakness in the arms and legs
* Fatigue and muscle tiredness
* Difficulty swallowing (dysphagia)
* Difficulty speaking or slurred speech (dysarthria)
* Drooping eyelids (ptosis)
* Double vision (diplopia)
* Weakness in the muscles of the face, arms, and legs

The exact cause of myasthenia gravis is not known, but it is believed to be an autoimmune disorder, meaning that the body's immune system mistakenly attacks healthy tissues. It can also be caused by other medical conditions such as thyroid disease, vitamin deficiencies, or infections.

There is no cure for myasthenia gravis, but there are various treatments available to manage the symptoms and improve quality of life. These include:

* Medications such as corticosteroids, immunosuppressants, and cholinesterase inhibitors
* Plasmapheresis, a procedure that removes harmful antibodies from the blood
* Intravenous immunoglobulin (IVIG), which contains antibodies that can help block the immune system's attack on the nerve-muscle junction
* Surgery to remove the thymus gland, which is believed to play a role in the development of myasthenia gravis

It is important for individuals with myasthenia gravis to work closely with their healthcare provider to manage their symptoms and prevent complications. With proper treatment and self-care, many people with myasthenia gravis are able to lead active and fulfilling lives.

Tobacco use disorder refers to a condition where an individual engages in the excessive and compulsive consumption of tobacco products, despite the negative consequences it may have on their health and well-being. Tobacco use disorder is a common condition that affects millions of people worldwide, and it is characterized by a pattern of continued tobacco use despite harmful effects, as well as an increased tolerance to tobacco and withdrawal symptoms when trying to stop.

The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) defines tobacco use disorder as a chronic condition that can manifest in different forms, including nicotine dependence and tobacco abuse. The criteria for diagnosing tobacco use disorder include:

1. Tolerance: A need to use more tobacco to achieve the desired effect.
2. Withdrawal: Experiencing symptoms such as irritability, anxiety, or depression when trying to stop using tobacco.
3. Loss of control: Consuming more tobacco than intended or for longer periods than intended.
4. Negative consequences: Continuing to use tobacco despite social, physical, or psychological problems caused by its use.
5. Increased time and effort spent on using tobacco.
6. Craving or a strong desire to use tobacco.
7. Failure to control or reduce tobacco use.

Tobacco use disorder can have severe consequences, including lung cancer, heart disease, respiratory problems, and other health issues. It can also lead to social and economic problems, such as lost productivity and strained relationships with family and friends. Treatment for tobacco use disorder includes behavioral therapies, medications, and support groups, and it is important for individuals struggling with this condition to seek professional help to quit using tobacco and improve their overall health and well-being.

There are several different types of congenital myasthenic syndromes, each with its own unique set of symptoms and characteristics. Some of the most common include:

* Congenital myasthenic syndrome type 1 (CMS1): This is the most common type of CMS and is caused by a mutation in the CHRNA1 gene. It is characterized by muscle weakness, poor feeding, and delays in development.
* Congenital myasthenic syndrome type 2 (CMS2): This type is caused by a mutation in the CHRNB1 gene and is characterized by muscle weakness, cognitive impairment, and seizures.
* Congenital myasthenic syndrome type 3 (CMS3): This type is caused by a mutation in the MAP2 gene and is characterized by muscle weakness, developmental delays, and intellectual disability.

There is currently no cure for congenital myasthenic syndromes, but various treatments can help manage the symptoms. These may include physical therapy, occupational therapy, speech therapy, and medications such as acetylcholinesterase inhibitors and steroids. In some cases, a bone marrow transplant may be necessary.

The prognosis for individuals with congenital myasthenic syndromes varies depending on the specific type and severity of the disorder. Some individuals may have mild symptoms and lead relatively normal lives, while others may have more severe symptoms and require ongoing medical care and support. With appropriate treatment and management, many individuals with CMS can lead fulfilling lives.

The frontal lobe is responsible for several higher-level cognitive functions, including decision-making, planning, and problem-solving. Therefore, FLE can significantly impact an individual's quality of life, particularly in terms of cognitive and behavioral functioning.

There are two main types of FLE:

1. Localization-related FLE: This type of epilepsy is characterized by seizures that arise from a specific location within the frontal lobe. The seizures may be limited to one side of the brain or may involve both sides.
2. Non-localization related FLE: This type of epilepsy is characterized by seizures that do not have a specific localization within the frontal lobe. Instead, the seizures may involve multiple areas of the frontal lobe or may be widespread throughout the brain.

The symptoms of FLE can vary depending on the location and extent of the seizure activity in the frontal lobe. Some common symptoms include:

* Confusion and disorientation
* Memory loss or difficulty with memory formation
* Difficulty with attention and concentration
* Slowing down of mental processing
* Impaired decision-making and problem-solving abilities
* Changes in mood or behavior, such as irritability or apathy
* Muscle weakness or stiffness
* Involuntary movements or tremors

FLE can be diagnosed using a variety of imaging techniques, such as electroencephalography (EEG), magnetic resonance imaging (MRI), and positron emission tomography (PET). Treatment options for FLE include medications, such as anticonvulsants and mood stabilizers, and surgical interventions, such as cortical resection or temporal lobectomy.

In summary, frontal lobe epilepsy is a complex condition that can have a significant impact on an individual's quality of life. It is important for individuals with FLE to work closely with their healthcare providers to develop a treatment plan that addresses their specific needs and helps to manage their symptoms. With appropriate treatment, many individuals with FLE are able to lead fulfilling lives.

Experimental myasthenia gravis refers to a type of myasthenia gravis that is caused by experimental or artificial means, such as through the use of drugs or other substances that mimic or trigger an immune response. This type of myasthenia gravis is often used in research settings to study the underlying mechanisms of the disease and to test new treatments.

Autoimmune myasthenia gravis, on the other hand, refers to a type of myasthenia gravis that is caused by an abnormal immune response, where the immune system mistakenly attacks the acetylcholine receptors at the neuromuscular junction. This type of myasthenia gravis is more common than experimental myasthenia gravis and can be caused by a variety of factors, such as genetic predisposition, infections, or environmental triggers.

Overall, myasthenia gravis, autoimmune, and experimental refer to different aspects of the disease, with each term having its own specific meaning and application in the medical field.

* Anxiety
* Depression
* Fatigue
* Insomnia
* Muscle and bone pain
* Nausea and vomiting
* Seizures (in severe cases)
* Sweating
* Tremors

The specific symptoms of substance withdrawal syndrome can vary depending on the substance being withdrawn from, but some common symptoms include:

* Alcohol: tremors, anxiety, insomnia, nausea and vomiting, headaches, and seizures
* Opioids: withdrawal symptoms can include anxiety, muscle aches, sweating, nausea and vomiting, diarrhea, and depression
* Benzodiazepines: withdrawal symptoms can include anxiety, insomnia, tremors, and seizures

The diagnosis of substance withdrawal syndrome is typically made based on the patient's history of substance use and the presence of withdrawal symptoms. A healthcare provider may also order laboratory tests to rule out other conditions that may be causing the symptoms. Treatment for substance withdrawal syndrome usually involves supportive care, such as rest, hydration, and pain management, as well as medication to manage withdrawal symptoms. In some cases, medical professionals may also recommend a gradual tapering of the substance over a period of time to minimize withdrawal symptoms.

It is important for individuals who are experiencing withdrawal symptoms to seek medical attention as soon as possible, as untreated withdrawal can lead to serious complications, such as seizures and dehydration. With appropriate treatment, most individuals with substance withdrawal syndrome can recover fully and successfully overcome their addiction.

1. Difficulty regulating body temperature, leading to episodes of hyperthermia (elevated body temperature) or hypothermia (low body temperature).
2. Abnormal heart rate and rhythm, including bradycardia (slow heart rate) or tachycardia (fast heart rate).
3. Poor digestion and gastrointestinal problems such as constipation, diarrhea, nausea, and vomiting.
4. Difficulty swallowing, which can lead to respiratory problems.
5. Orthostatic intolerance, which can cause dizziness, lightheadedness, or fainting when standing up.
6. Seizures and other neurological symptoms such as tremors, muscle weakness, and loss of coordination.
7. Cognitive impairment, including developmental delays, intellectual disability, and learning disabilities.
8. Sleep disturbances, including insomnia and sleep apnea.
9. Emotional difficulties such as anxiety, depression, and mood swings.
10. Vision problems, including blurred vision, double vision, and light sensitivity.

Primary dysautonomias are caused by genetic mutations that affect the development or function of the autonomic nervous system. There are several subtypes of primary dysautonomias, each with distinct symptoms and characteristics. These conditions are rare and can be difficult to diagnose, as they often resemble other more common conditions such as anxiety disorders or attention deficit hyperactivity disorder (ADHD). Treatment for primary dysautonomias typically involves a combination of medication and lifestyle modifications, such as reducing stress, increasing fluid intake, and avoiding overexertion. In some cases, surgery may be necessary to correct anatomical abnormalities or to implant medical devices that help regulate the autonomic nervous system.

Some common autoimmune diseases of the nervous system include:

1. Multiple sclerosis (MS): A chronic condition that affects the brain, spinal cord, and optic nerves, causing a range of symptoms including numbness, weakness, and vision problems.
2. Neuromyelitis optica (NMO): A rare condition that causes inflammation in the optic nerves and spinal cord, leading to vision loss and muscle weakness.
3. Guillain-Barré syndrome: A rare autoimmune disorder that causes muscle weakness and paralysis, often after a viral infection.
4. Chronic inflammatory demyelinating polyneuropathy (CIDP): A chronic condition that affects the peripheral nerves, causing numbness, weakness, and pain in the hands and feet.
5. Acute disseminated encephalomyelitis (ADEM): A rare condition that causes inflammation in the brain and spinal cord, leading to a range of symptoms including fever, headache, and muscle weakness.

The exact cause of autoimmune diseases of the nervous system is not fully understood, but they are believed to be triggered by a combination of genetic and environmental factors. Treatment options vary depending on the specific condition, but may include medications to reduce inflammation and modulate the immune system, as well as physical therapy and lifestyle modifications.

1) They share similarities with humans: Many animal species share similar biological and physiological characteristics with humans, making them useful for studying human diseases. For example, mice and rats are often used to study diseases such as diabetes, heart disease, and cancer because they have similar metabolic and cardiovascular systems to humans.

2) They can be genetically manipulated: Animal disease models can be genetically engineered to develop specific diseases or to model human genetic disorders. This allows researchers to study the progression of the disease and test potential treatments in a controlled environment.

3) They can be used to test drugs and therapies: Before new drugs or therapies are tested in humans, they are often first tested in animal models of disease. This allows researchers to assess the safety and efficacy of the treatment before moving on to human clinical trials.

4) They can provide insights into disease mechanisms: Studying disease models in animals can provide valuable insights into the underlying mechanisms of a particular disease. This information can then be used to develop new treatments or improve existing ones.

5) Reduces the need for human testing: Using animal disease models reduces the need for human testing, which can be time-consuming, expensive, and ethically challenging. However, it is important to note that animal models are not perfect substitutes for human subjects, and results obtained from animal studies may not always translate to humans.

6) They can be used to study infectious diseases: Animal disease models can be used to study infectious diseases such as HIV, TB, and malaria. These models allow researchers to understand how the disease is transmitted, how it progresses, and how it responds to treatment.

7) They can be used to study complex diseases: Animal disease models can be used to study complex diseases such as cancer, diabetes, and heart disease. These models allow researchers to understand the underlying mechanisms of the disease and test potential treatments.

8) They are cost-effective: Animal disease models are often less expensive than human clinical trials, making them a cost-effective way to conduct research.

9) They can be used to study drug delivery: Animal disease models can be used to study drug delivery and pharmacokinetics, which is important for developing new drugs and drug delivery systems.

10) They can be used to study aging: Animal disease models can be used to study the aging process and age-related diseases such as Alzheimer's and Parkinson's. This allows researchers to understand how aging contributes to disease and develop potential treatments.

Mydriasis is a condition where the pupil remains dilated for an extended period, even in low light conditions. It can be caused by various factors such as injury to the head or eye, stroke, brain tumors, multiple sclerosis, and certain medications. Mydriasis can cause problems with vision, including blurred vision, double vision, and sensitivity to light. Treatment options for mydriasis depend on the underlying cause, but may include glasses or contact lenses to correct refractive errors, prism lenses to align images properly, or medications to reduce inflammation or treat underlying conditions.

Causes of Mydriasis
------------------

Mydriasis can be caused by a variety of factors, including:

1. Trauma to the head or eye: A blow to the head or a penetrating eye injury can cause mydriasis due to damage to the nerves that control pupil size.
2. Stroke or cerebral vasculature disorders: A stroke or other conditions that affect blood flow to the brain can cause mydriasis due to damage to the nerves that control pupillary constriction.
3. Brain tumors: Tumors in the brain, such as melanoma, can cause mydriasis by compressing or damaging the nerves that control pupil size.
4. Multiple sclerosis: This autoimmune disease can damage the nerves that control pupillary constriction, leading to mydriasis.
5. Medications: Certain medications, such as anticholinergic drugs and certain antihistamines, can cause mydriasis as a side effect.

Symptoms of Mydriasis
--------------------

The symptoms of mydriasis may include:

1. Dilated pupils that do not constrict in response to light
2. Blurred vision or double vision
3. Sensitivity to light
4. Headaches or eye strain
5. Seeing halos around lights
6. Difficulty seeing at night or in low light conditions
7. Nausea and vomiting

Diagnosis of Mydriasis
---------------------

To diagnose mydriasis, a comprehensive eye exam is necessary to rule out other causes of dilated pupils. The doctor may perform a series of tests to evaluate the function of the nervous system and the muscles that control pupillary constriction. These tests may include:

1. Pupillometry: This test measures the size of the pupils and their reaction to light.
2. Ophthalmoscopy: This test allows the doctor to visualize the inside of the eye and assess the function of the retina and optic nerve.
3. Eye movement testing: This test evaluates the muscles that control eye movement and their coordination with the pupillary constriction reflex.
4. Neurological exam: A neurological exam may be performed to rule out other conditions that can cause dilated pupils, such as brain tumors or multiple sclerosis.

Treatment of Mydriasis
---------------------

The treatment of mydriasis depends on the underlying cause of the condition. In some cases, treating the underlying condition can resolve the mydriasis. Other treatments that may be used to manage mydriasis include:

1. Pupillary constriction medications: These medications can help reduce the size of dilated pupils and improve vision.
2. Prism glasses: In some cases, prism glasses may be prescribed to help align the visual fields and improve binocular vision.
3. Eye exercises: Eye exercises may be recommended to strengthen the muscles that control eye movement and improve coordination between the pupils.
4. Surgery: In rare cases, surgery may be necessary to treat mydriasis caused by a physical obstruction or other abnormality in the eye.

Prognosis of Mydriasis
---------------------

The prognosis for mydriasis is generally good if the underlying cause is treated promptly and effectively. However, if the condition is left untreated, it can lead to complications such as:

1. Vision loss: Prolonged dilated pupils can lead to vision loss due to retinal damage or optic nerve damage.
2. Eye strain: Dilated pupils can cause eye strain and fatigue, which can lead to headaches and other symptoms.
3. Increased risk of eye injuries: Dilated pupils may increase the risk of eye injuries, as the pupil is more vulnerable to trauma when it is dilated.
4. Increased risk of infection: Dilated pupils may increase the risk of infection, as the pupil is more exposed to foreign substances and bacteria.

Prevention of Mydriasis
----------------------

There are several steps you can take to help prevent mydriasis:

1. Get regular eye exams: Regular eye exams can help detect any underlying conditions that may be causing dilated pupils, such as cataracts or glaucoma.
2. Wear protective eyewear: Wearing protective eyewear, such as goggles or safety glasses, can help prevent eye injuries and reduce the risk of mydriasis.
3. Avoid exposure to bright lights: Bright lights can cause dilated pupils, so it is best to avoid exposure to bright lights, especially during the day.
4. Use artificial tears: Artificial tears can help keep the eyes moist and reduce the risk of mydriasis.
5. Get enough sleep: Getting enough sleep can help prevent eye strain and fatigue, which can lead to mydriasis.
6. Take breaks when working on a computer: Taking breaks when working on a computer can help reduce eye strain and fatigue, which can lead to mydriasis.
7. Use good lighting: Good lighting can help reduce eye strain and fatigue, which can lead to mydriasis.
8. Avoid smoking: Smoking can increase the risk of mydriasis, so it is best to avoid smoking.
9. Maintain good hygiene: Maintaining good hygiene, such as washing your hands frequently and avoiding sharing makeup or other products, can help prevent infection and reduce the risk of mydriasis.

Conclusion
----------

Mydriasis is a common condition that can cause eye strain and fatigue, as well as increase the risk of eye injuries and infection. There are several steps you can take to prevent mydriasis, including avoiding smoking, getting enough sleep, using artificial tears, and taking breaks when working on a computer. Additionally, maintaining good hygiene and using good lighting can help reduce the risk of mydriasis. If you experience any symptoms of mydriasis, it is important to seek medical attention as soon as possible to prevent complications.

The term "schizophrenia" was first used by the Swiss psychiatrist Eugen Bleuler in 1908 to describe the splitting of mental functions, which he believed was a key feature of the disorder. The word is derived from the Greek words "schizein," meaning "to split," and "phrenos," meaning "mind."

There are several subtypes of schizophrenia, including:

1. Paranoid Schizophrenia: Characterized by delusions of persecution and suspicion, and a tendency to be hostile and defensive.
2. Hallucinatory Schizophrenia: Characterized by hearing voices or seeing things that are not there.
3. Disorganized Schizophrenia: Characterized by disorganized thinking and behavior, and a lack of motivation or interest in activities.
4. Catatonic Schizophrenia: Characterized by immobility, mutism, and other unusual movements or postures.
5. Undifferentiated Schizophrenia: Characterized by a combination of symptoms from the above subtypes.

The exact cause of schizophrenia is still not fully understood, but it is believed to involve a combination of genetic, environmental, and neurochemical factors. It is important to note that schizophrenia is not caused by poor parenting or a person's upbringing.

There are several risk factors for developing schizophrenia, including:

1. Genetics: A person with a family history of schizophrenia is more likely to develop the disorder.
2. Brain chemistry: Imbalances in neurotransmitters such as dopamine and serotonin have been linked to schizophrenia.
3. Prenatal factors: Factors such as maternal malnutrition or exposure to certain viruses during pregnancy may increase the risk of schizophrenia in offspring.
4. Childhood trauma: Traumatic events during childhood, such as abuse or neglect, have been linked to an increased risk of developing schizophrenia.
5. Substance use: Substance use has been linked to an increased risk of developing schizophrenia, particularly cannabis and other psychotic substances.

There is no cure for schizophrenia, but treatment can help manage symptoms and improve quality of life. Treatment options include:

1. Medications: Antipsychotic medications are the primary treatment for schizophrenia. They can help reduce positive symptoms such as hallucinations and delusions, and negative symptoms such as a lack of motivation or interest in activities.
2. Therapy: Cognitive-behavioral therapy (CBT) and other forms of talk therapy can help individuals with schizophrenia manage their symptoms and improve their quality of life.
3. Social support: Support from family, friends, and support groups can be an important part of the treatment plan for individuals with schizophrenia.
4. Self-care: Engaging in activities that bring pleasure and fulfillment, such as hobbies or exercise, can help individuals with schizophrenia improve their overall well-being.

It is important to note that schizophrenia is a complex condition, and treatment should be tailored to the individual's specific needs and circumstances. With appropriate treatment and support, many people with schizophrenia are able to lead fulfilling lives and achieve their goals.

Types of NMJ Diseases:

1. Myasthenia Gravis (MG): An autoimmune disorder that causes muscle weakness and fatigue due to the immune system attacking the NMJs.
2. Lambert-Eaton Myasthenic Syndrome (LEMS): A rare autoimmune disorder that affects the NMJ and can cause muscle weakness, fatigue, and other symptoms.
3. Congenital Myasthenic Syndromes (CMS): A group of rare genetic disorders that affect the development and function of the NMJ, leading to muscle weakness and other symptoms.
4. Neuronal Ceroid Lipofuscinosis (NCL): A group of rare genetic disorders that affect the nervous system and can cause muscle weakness, seizures, and vision loss.
5. Inflammatory Myopathies: A group of muscle disorders caused by inflammation, such as polymyositis or dermatomyositis, which can affect the NMJ and cause muscle weakness.

Symptoms of NMJ Diseases:

1. Muscle weakness or paralysis
2. Fatigue and exhaustion
3. Difficulty swallowing or breathing (in severe cases)
4. Droopy eyelids or double vision
5. Slurred speech or difficulty speaking
6. Weakness in the arms and legs
7. Muscle wasting and loss of muscle mass
8. Seizures or fits
9. Vision loss or blurred vision
10. Cramps or spasms

Diagnosis of NMJ Diseases:

1. Medical history and physical examination
2. Electromyography (EMG) to test muscle activity and strength
3. Nerve conduction studies (NCS) to test nerve function
4. Imaging tests such as MRI or CT scans to rule out other conditions
5. Blood tests to check for autoantibodies or other signs of inflammation
6. Genetic testing to diagnose inherited forms of NMJ diseases

Treatment of NMJ Diseases:

1. Medications such as steroids, immunosuppressants, and anticonvulsants to reduce inflammation and muscle weakness
2. Physical therapy to improve muscle strength and function
3. Occupational therapy to improve daily living skills
4. Speech therapy to improve communication and swallowing difficulties
5. Surgery to relieve compression or repair damaged nerves or muscles
6. Plasmapheresis (plasma exchange) to remove harmful antibodies from the blood
7. Intravenous immunoglobulin (IVIG) therapy to reduce inflammation and modulate the immune system
8. Immunoadsorption therapy to remove antibodies from the blood and restore immune balance
9. Stem cell transplantation to replace damaged cells with healthy ones
10. Gene therapy to repair genetic defects causing NMJ diseases.

It's important to note that the treatment of NMJ diseases is highly individualized and may vary depending on the specific diagnosis, severity of symptoms, and overall health of the patient. A multidisciplinary approach involving neurologists, physical therapists, occupational therapists, speech therapists, and other specialists may be necessary to provide comprehensive care.

There are many different types of ANS diseases, including:

1. Dysautonomia: a general term that refers to dysfunction of the autonomic nervous system.
2. Postural orthostatic tachycardia syndrome (POTS): a condition characterized by rapid heart rate and other symptoms that occur upon standing.
3. Neurocardiogenic syncope: a form of fainting caused by a sudden drop in blood pressure.
4. Multiple system atrophy (MSA): a progressive neurodegenerative disorder that affects the autonomic nervous system and other parts of the brain.
5. Parkinson's disease: a neurodegenerative disorder that can cause autonomic dysfunction, including constipation, urinary incontinence, and erectile dysfunction.
6. Dopamine deficiency: a condition characterized by low levels of the neurotransmitter dopamine, which can affect the ANS and other body systems.
7. Autonomic nervous system disorders associated with autoimmune diseases, such as Guillain-Barré syndrome and lupus.
8. Trauma: physical or emotional trauma can sometimes cause dysfunction of the autonomic nervous system.
9. Infections: certain infections, such as Lyme disease, can affect the autonomic nervous system.
10. Genetic mutations: some genetic mutations can affect the functioning of the autonomic nervous system.

Treatment for ANS diseases depends on the specific condition and its underlying cause. In some cases, medication may be prescribed to regulate heart rate, blood pressure, or other bodily functions. Lifestyle changes, such as regular exercise and stress management techniques, can also be helpful in managing symptoms. In severe cases, surgery may be necessary to correct anatomical abnormalities or repair damaged nerves.

The symptoms of catatonia can vary widely and may include:

1. Immobility: The patient may remain in a fixed position for extended periods of time, even when asked to move or perform tasks.
2. Mutism: The patient may be unable to speak, or may speak very little, despite being able to understand speech and communicate non-verbally.
3. Negativism: The patient may resist instructions or commands given by others, often in a passive-aggressive manner.
4. Perseveration: The patient may persist in performing a task or action that is no longer appropriate or relevant.
5. Stereotypy: The patient may exhibit repetitive and purposeless movements, such as rocking or pacing.
6. Posturing: The patient may assume and maintain abnormal postures, such as holding their arms or legs in unusual positions.
7. Oculogyric crisis: A sudden, sustained upward deviation of the eyes, often accompanied by neck stiffness and resistance to movement.
8. Echolalia: The patient may repeat words or phrases spoken by others, often in a echoing or parrot-like manner.
9. Echopraxia: The patient may imitate the movements of others, such as facial expressions or gestures.

The exact cause of catatonia is not fully understood, but it is thought to be related to dysfunction in certain areas of the brain, including the basal ganglia and the cortex. It can be triggered by a variety of factors, such as stress, trauma, infections, or certain medications.

Treatment for catatonia usually involves a combination of pharmacological and behavioral interventions. Benzodiazepines, such as lorazepam, are often used to help manage agitation and psychomotor agitation, while antipsychotic medications, such as haloperidol, can be effective in reducing positive symptoms. Electroconvulsive therapy (ECT) may also be considered in severe cases that do not respond to other treatments. Behavioral interventions, such as cognitive-behavioral therapy and behavioral activation, can help patients with catatonia to develop more adaptive coping strategies and improve their overall functioning.

Neuroblastoma is caused by a genetic mutation that affects the development and growth of nerve cells. The cancerous cells are often sensitive to chemotherapy, but they can be difficult to remove surgically because they are deeply embedded in the nervous system.

There are several different types of neuroblastoma, including:

1. Infantile neuroblastoma: This type of neuroblastoma occurs in children under the age of one and is often more aggressive than other types of the cancer.
2. Juvenile neuroblastoma: This type of neuroblastoma occurs in children between the ages of one and five and tends to be less aggressive than infantile neuroblastoma.
3. Adult neuroblastoma: This type of neuroblastoma occurs in adults and is rare.
4. Metastatic neuroblastoma: This type of neuroblastoma has spread to other parts of the body, such as the bones or liver.

Symptoms of neuroblastoma can vary depending on the location and size of the tumor, but they may include:

* Abdominal pain
* Fever
* Loss of appetite
* Weight loss
* Fatigue
* Bone pain
* Swelling in the abdomen or neck
* Constipation
* Increased heart rate

Diagnosis of neuroblastoma typically involves a combination of imaging tests, such as CT scans and MRI scans, and biopsies to confirm the presence of cancerous cells. Treatment for neuroblastoma usually involves a combination of chemotherapy, surgery, and radiation therapy. The prognosis for neuroblastoma varies depending on the type of cancer, the age of the child, and the stage of the disease. In general, the younger the child and the more aggressive the treatment, the better the prognosis.

CHRNA7, coding the neuronal nicotinic acetylcholine receptor alpha7 subunit. alpha7-containing receptors are known to improve ... Leiser SC, Bowlby MR, Comery TA, Dunlop J (June 2009). "A cog in cognition: how the alpha 7 nicotinic acetylcholine receptor is ... "The effect of genetic variation of the serotonin 1B receptor gene on impulsive aggressive behavior and suicide". American ... basis for one of these at-risk endophenotypes has been suggested in 2007 to be the gene coding for the serotonin receptor 5- ...

https://en.wikipedia.org/wiki/Endophenotype

February 2009). "alpha7 and non-alpha7 nicotinic acetylcholine receptors modulate dopamine release in vitro and in vivo in the ... Young GT, Zwart R, Walker AS, Sher E, Millar NS (September 2008). "Potentiation of alpha7 nicotinic acetylcholine receptors via ... April 2005). "A novel positive allosteric modulator of the alpha7 neuronal nicotinic acetylcholine receptor: in vitro and in ... "Glutamate-dopamine crosstalk in the rat prefrontal cortex is modulated by Alpha7 nicotinic receptors and potentiated by PNU- ...

https://en.wikipedia.org/wiki/PNU-120,596

Alpha-7 nicotinic receptor Nicotinic acetylcholine receptor Acetylcholine receptor ENSG00000175344, ENSG00000282088 GRCh38: ... The protein encoded by this gene is a subunit of certain nicotinic acetylcholine receptors (nAchR). The nicotinic acetylcholine ... "Diversity of mRNA expression for muscarinic acetylcholine receptor subtypes and neuronal nicotinic acetylcholine receptor ... binds to alpha7 nicotinic acetylcholine receptor with high affinity. Implications for Alzheimer's disease pathology". J. Biol. ...

https://en.wikipedia.org/wiki/CHRNA7

The monomeric form can bind with high affinity to muscular, Torpedo, and neuronal alpha-7 nicotinic acetylcholine receptors ( ... It is a nicotinic acetylcholine receptor (nAChR) antagonist which causes paralysis by preventing the binding of acetylcholine ... "Role of alpha7-nicotinic acetylcholine receptor in human non-small cell lung cancer proliferation". Cell Proliferation. 41 (6 ... and structure activity of a highly selective alpha7 nicotinic acetylcholine receptor antagonist". Biochemistry. 46 (22): 6628- ...

https://en.wikipedia.org/wiki/Cobratoxin

Redrobe, J (2009). "Alpha7 nicotinic acetylcholine receptor activation ameliorates scopolamine-induced behavioural changes in a ... Hansen, H.; Timmermann, D.; Peters, D.; Walters, C.; Damaj, M.; Mikkelsen, J. (2007). "Alpha-7 nicotinic acetylcholine receptor ... "The selective alpha7 nicotinic acetylcholine receptor agonist PNU-282987 N-(3R)-1-Azabicyclo2.2.2oct-3-yl-4-chlorobenzamide ... and in vivo activity of azabicyclic aryl amides as alpha7 nicotinic acetylcholine receptor agonists". Bioorg. Med. Chem. 14 (24 ...

https://en.wikipedia.org/wiki/PNU-282,987

April 2005). "A novel positive allosteric modulator of the alpha7 neuronal nicotinic acetylcholine receptor: in vitro and in ... Nicotinic acetylcholine receptors are the best-studied of the ionotropic receptors. Since nicotinic receptors help transmit ... The nicotinic receptors are considered cholinergic receptors, since they respond to acetylcholine. Nicotinic receptors get ... Acetylcholine itself binds to both muscarinic and nicotinic acetylcholine receptors. As ionotropic receptors, nAChRs are ...

https://en.wikipedia.org/wiki/Nicotinic_acetylcholine_receptor

"Evidence of BrdU-positive retinal neurons after application of an Alpha7 nicotinic acetylcholine receptor agonist". ...

https://en.wikipedia.org/wiki/Retinal_regeneration

"Evidence of BrdU-positive retinal neurons after application of an Alpha7 nicotinic acetylcholine receptor agonist". ... the activation of stem cells following administration of α7 nicotinic acetylcholine receptor agonist, PNU-282987, has been ... Eph receptors and ephrin signaling have been shown to regulate adult neurogenesis in the hippocampus and have been studied as ... Han, S.; Zhao, B.; Pan, X.; Song, Z.; Liu, J.; Gong, Y.; Wang, M. (2015-12-03). "Estrogen receptor variant ER-α36 is involved ...

https://en.wikipedia.org/wiki/Adult_neurogenesis

2005). "Ric-3 promotes functional expression of the nicotinic acetylcholine receptor alpha7 subunit in mammalian cells". J. ... particularly the homomeric α7 nicotinic receptor. RIC-3 enhances currents generated by these receptors by expediting receptor ... Effectors of mammalian nicotinic acetylcholine receptor expression". J Biol Chem. 278 (36): 34411-7. doi:10.1074/jbc.M300170200 ... 2005). "Dual role of the RIC-3 protein in trafficking of serotonin and nicotinic acetylcholine receptors". J. Biol. Chem. 280 ( ...

https://en.wikipedia.org/wiki/RIC3

2004). "Alpha7-nicotinic acetylcholine receptors affect growth regulation of human mesothelioma cells: role of mitogen- ... 1998). "Genomic organization and partial duplication of the human alpha7 neuronal nicotinic acetylcholine receptor gene (CHRNA7 ... "A 3-Mb map of a large Segmental duplication overlapping the alpha7-nicotinic acetylcholine receptor gene (CHRNA7) at human ... "Linkage disequilibrium for schizophrenia at the chromosome 15q13-14 locus of the alpha7-nicotinic acetylcholine receptor ...

https://en.wikipedia.org/wiki/CHRFAM7A

... alpha4beta2 and alpha4beta4 nicotinic acetylcholine receptors". Journal of Neurochemistry. 78 (5): 1029-43. doi:10.1046/j.1471- ... September 2001). "Activity of cytisine and its brominated isosteres on recombinant human alpha7, ... is a derivative of the toxic alkaloid cytisine that acts as a highly potent agonist at neural nicotinic acetylcholine receptors ... April 2006). "C3-halogenation of cytisine generates potent and efficacious nicotinic receptor agonists". European Journal of ...

https://en.wikipedia.org/wiki/3-Bromocytisine

"Postsynaptic action of brain-derived neurotrophic factor attenuates alpha7 nicotinic acetylcholine receptor-mediated responses ... It may also modulate the activity of various neurotransmitter receptors, including the Alpha-7 nicotinic receptor. BDNF has ... The TrkB receptor is encoded by the NTRK2 gene and is member of a receptor family of tyrosine kinases that includes TrkA and ... While the TrkB receptor interacts with BDNF in a ligand-specific manner, all neurotrophins can interact with the p75 receptor. ...

https://en.wikipedia.org/wiki/Brain-derived_neurotrophic_factor

May 2009). "Procognitive and neuroprotective activity of a novel alpha7 nicotinic acetylcholine receptor agonist for treatment ... July 2009). "SAR and biological evaluation of SEN12333/WAY-317538: Novel alpha 7 nicotinic acetylcholine receptor agonist". ... is a drug that acts as a potent and selective full agonist for the α7 subtype of neural nicotinic acetylcholine receptors. It ... but was selected for further development on the basis of its high selectivity over related receptors, ease of synthesis, and ...

https://en.wikipedia.org/wiki/WAY-317538

miR-590 downregulation has further been shown to be mediated by activation of alpha-7 nicotinic acetylcholine receptors (α7- ... This downregulation sees the removal of post-transcriptional repression of TGF-β1 and TGF-β receptor type II (TGF-βRII), and ...

https://en.wikipedia.org/wiki/Mir-590_microRNA_precursor_family

A positive allosteric effector of the alpha7 neuronal nicotinic acetylcholine receptor". Molecular Pharmacology. 53 (2): 283-94 ... The ion channel of the nicotinic acetylcholine receptor is formed by the homologous helices M II of the receptor subunits. FEBS ... 2004) Nicotinic Acetylcholine Receptors: From Molecular Biology to Cognition Changeux, Jean-Pierre. (2002) L'homme de verite ( ... Edelstein S., Schaad O., Henry E., Bertrand D. Changeux J.-P. (1996). A kinetic mechanism for nicotinic acetylcholine receptors ...

https://en.wikipedia.org/wiki/Jean-Pierre_Changeux

The protein encoded by this gene is a subunit of certain nicotinic acetylcholine receptors (nAchR). Nicotinic acetylcholine ... and alpha7 subunits". Biochem. Biophys. Res. Commun. 268 (2): 480-4. doi:10.1006/bbrc.2000.2155. PMID 10679230. Groot-Kormelink ... nicotinic, alpha 5". Hung et al. A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes ... 1997). "Comparative structure of human neuronal alpha 2-alpha 7 and beta 2-beta 4 nicotinic acetylcholine receptor subunits and ...

https://en.wikipedia.org/wiki/CHRNA5

Aracava Y, Pereira EF, Maelicke A, Albuquerque EX (March 2005). "Memantine blocks alpha7* nicotinic acetylcholine receptors ... Memantine acts as a non-competitive antagonist at different neuronal nicotinic acetylcholine receptors (nAChRs) at potencies ... Buisson B, Bertrand D (March 1998). "Open-channel blockers at the human alpha4beta2 neuronal nicotinic acetylcholine receptor ... It has been shown that the number of nicotinic receptors in the brain are reduced in Alzheimer's disease, even in the absence ...

https://en.wikipedia.org/wiki/Memantine

... or alpha7-nicotinic acetylcholine receptor subunit knockout mice". Psychopharmacology. 189 (3): 395-401. doi:10.1007/s00213-006 ... Bacher I, Wu B, Shytle DR, George TP (November 2009). "Mecamylamine - a nicotinic acetylcholine receptor antagonist with ... non-competitive antagonist of the nicotinic acetylcholine receptors (nAChRs) that was introduced in the 1950s as an ... This effect is thought to be due to its blocking α3β4 nicotinic receptors in the brain. It has also been reported to bring ...

https://en.wikipedia.org/wiki/Mecamylamine

... the neurotransmitter that inhibits cytokine release by interacting with alpha7 nicotinic acetylcholine receptors (CHRNA7) ... These cells present receptors contained on the surface or within the cell, named pattern recognition receptors (PRRs), which ... Viral components are recognized by different receptors: Toll-like receptors are located in the endosomal membrane and recognize ... The various subsets may be considered part of the innate immune system where a restricted TCR or NK receptors may be used as a ...

https://en.wikipedia.org/wiki/Innate_immune_system

... positive allosteric modulation of the alpha7 nicotinic acetylcholine receptor by the 5-hydroxytryptamine(2B/C) receptor ... 5-Hydroxytryptamine receptor 2B (5-HT2B) also known as serotonin receptor 2B is a protein that in humans is encoded by the ... The 5-HT2 receptors (of which the 5-HT2B receptor is a subtype) mediate many of the central and peripheral physiologic ... These receptors are also overexpressed in human failing heart and antagonists of 5-HT2B receptors were uncovered to prevent ...

https://en.wikipedia.org/wiki/5-HT2B_receptor

... an agonist of the alpha7 nicotinic acetylcholine receptor, for the potential treatment of cognitive deficits in schizophrenia: ... "Cognitive Enhancer Effects of Low Memantine Doses Are Facilitated by an Alpha7 Nicotinic Acetylcholine Receptor Agonist in ... Ji L, Chen Y, Wei H, Feng H, Chang R, Yu D, Wang X, Gong X, Zhang M (July 2019). "Activation of alpha7 acetylcholine receptors ... Krafft PR, Altay O, Rolland WB, Duris K, Lekic T, Tang J, Zhang JH (March 2012). "α7 nicotinic acetylcholine receptor agonism ...

https://en.wikipedia.org/wiki/PHA-543,613

... sensory overload in schizophrenic patients is that abnormalities in alpha-7 and low affinity nicotinic acetylcholine receptors ... Deep pressure against the skin combined with proprioceptive input that stimulates the receptors in the joints and ligaments ... These sensitivities are partially explained by abnormal neurotransmitter pathways involving serotonin and acetylcholine. When ...

https://en.wikipedia.org/wiki/Sensory_overload

... positive allosteric modulation of the alpha7 nicotinic acetylcholine receptor by the 5-hydroxytryptamine(2B/C) receptor ... It has also been shown to act as a positive allosteric modulator of α7 nicotinic acetylcholine receptors. Modified derivatives ... SB-206553 is a drug which acts as a mixed antagonist for the 5-HT2B and 5-HT2C serotonin receptors. It has anxiolytic ... Canal CE, Olaghere da Silva UB, Gresch PJ, Watt EE, Sanders-Bush E, Airey DC (April 2010). "The serotonin 2C receptor potently ...

https://en.wikipedia.org/wiki/SB-206553

The alpha-7 nicotinic receptor, also known as the α7 receptor, is a type of nicotinic acetylcholine receptor implicated in long ... α7 subtype preferring blocker α3β2-Nicotinic receptor α3β4-Nicotinic receptor α4β2-Nicotinic receptor RIC3, a chaperone protein ... April 2005). "A novel positive allosteric modulator of the alpha7 neuronal nicotinic acetylcholine receptor: in vitro and in ... June 2007). "Discovery, synthesis, and structure activity of a highly selective alpha7 nicotinic acetylcholine receptor ...

https://en.wikipedia.org/wiki/Alpha-7_nicotinic_receptor

... and the Alpha-7 nicotinic receptor receptor expressed on cytokine-producing cells. The release of acetylcholine in spleen ... 2011). "Acetylcholine-Synthesizing T Cells Relay Neural Signals in a Vagus Nerve Circuit". Science. 334 (6052): 98-101. Bibcode ... where a subset of specialized T cells are activated to secrete acetylcholine. The net effect of the reflex is to prevent the ... extend the immunological memory The molecular basis of cytokine-inhibiting signals requires the neurotransmitter acetylcholine ...

https://en.wikipedia.org/wiki/Inflammatory_reflex

Li Y, Meyer EM, Walker DW, Millard WJ, He YJ, King MA (May 2002). "Alpha7 nicotinic receptor activation inhibits ethanol- ... de Fiebre NC, de Fiebre CM (November 2003). "Alpha 7 nicotinic acetylcholine receptor-mediated protection against ethanol- ... Martin LF, Kem WR, Freedman R (June 2004). "Alpha-7 nicotinic receptor agonists: potential new candidates for the treatment of ... Kem WR (August 2000). "The brain alpha7 nicotinic receptor may be an important therapeutic target for the treatment of ...

https://en.wikipedia.org/wiki/GTS-21

De Luca V, Wang H, Squassina A, Wong GW, Yeomans J, Kennedy JL (2004). "Linkage of M5 muscarinic and alpha7-nicotinic receptor ... "Diversity of mRNA expression for muscarinic acetylcholine receptor subtypes and neuronal nicotinic acetylcholine receptor ... 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". ...

https://en.wikipedia.org/wiki/Muscarinic_acetylcholine_receptor_M5

January 2007). "SSR180711, a novel selective alpha7 nicotinic receptor partial agonist: (II) efficacy in experimental models ... is a drug that acts as a potent and selective partial agonist for the α7 subtype of neural nicotinic acetylcholine receptors. ... January 2007). "SSR180711, a novel selective alpha7 nicotinic receptor partial agonist: (1) binding and functional profile". ... deficits in mice are improved by subsequent subchronic administration of the novel selective alpha7 nicotinic receptor agonist ...

https://en.wikipedia.org/wiki/SSR-180,711

Nicotinic Alpha7 Acetylcholine Receptor Agonist Program Archived 2010-01-07 at the Wayback Machine Rollema, H.; Chambers, L.K; ... The development of nicotinic acetylcholine receptor agonists has come a long way since then. Nicotinic acetylcholine receptor ... Muscarinic acetylcholine receptor Muscarinic agonist Muscarinic antagonist Nicotinic acetylcholine receptor Nicotinic ... A nicotinic agonist is a drug that mimics the action of acetylcholine (ACh) at nicotinic acetylcholine receptors (nAChRs). The ...

https://en.wikipedia.org/wiki/Nicotinic_agonist

The alpha-3 beta-2 nicotinic receptor, also known as the α3β2 receptor, is a type of nicotinic acetylcholine receptor, ... "Varenicline is a partial agonist at alpha4beta2 and a full agonist at alpha7 neuronal nicotinic receptors". Mol. Pharmacol. 70 ... 300 fold more potent on α3β2 than α6/α3β2β3 Tubocurarine α3β4-Nicotinic receptor α4β2-Nicotinic receptor α7-Nicotinic receptor ... Faraone, Stephen (2004). "A Novel Permutation Testing Method Implicates Sixteen Nicotinic Acetylcholine Receptor Genes as Risk ...

https://en.wikipedia.org/wiki/Alpha-3_beta-2_nicotinic_receptor

The alpha-4 beta-2 nicotinic receptor, also known as the α4β2 receptor, is a type of nicotinic acetylcholine receptor ... "Synthesis of desformylflustrabromine and its evaluation as an alpha4beta2 and alpha7 nACh receptor modulator". Bioorg. Med. ... Oxantel α3β2-Nicotinic receptor α3β4-Nicotinic receptor α6β2-Nicotinic receptor α7-Nicotinic receptor Cordero-Erausquin, M; ... HS receptors) (α4)3(β2)2 receptors have low sensitivity to nicotine and high Ca2+ permeability (LS receptors) The α4β2 receptor ...

https://en.wikipedia.org/wiki/Alpha-4_beta-2_nicotinic_receptor

It is a negative-allosteric modulator of the alpha-7 nicotinic receptor. It binds at a site distant from the traditional ... is an anxiolytic drug that acts via negative allosteric modulation of the α7-nicotinic acetylcholine receptor, by Bionomics ... The α7 subtype of the Nicotinic Acetylcholine is heavily represented in the amygdala (along with the mammary bodies (brain ... Acetylcholine, while being used very widely and commonly in mammals, is especially prominent in the function of memory and Long ...

https://en.wikipedia.org/wiki/BNC-210

A Structure-Activity Study on Its Ability To Potentiate the Action of Acetylcholine at α4β2 Nicotinic Acetylcholine Receptors ... "Synthesis of desformylflustrabromine and its evaluation as an alpha4beta2 and alpha7 nACh receptor modulator". Bioorganic & ... A Structure-Activity Study on Its Ability To Potentiate the Action of Acetylcholine at α4β2 Nicotinic Acetylcholine Receptors ... dFBr has been identified as a novel positive allosteric modulator of neuronal nicotinic acetylcholine receptor with sub-type ...

https://en.wikipedia.org/wiki/Desformylflustrabromine

It acts as a selective positive allosteric modulator of the α7 nicotinic acetylcholine receptor (nAChR). It does not act on the ... "Allosteric alpha-7 nicotinic receptor modulation and P50 sensory gating in schizophrenia: a proof-of-mechanism study". ... α4β2 or α3β4 nAChRs or the serotonin 5-HT3 receptor, and does not interact with a panel of 62 other receptors and enzymes. The ... Nicotinic antagonists, Nootropics, Propionamides, 4-Pyridyl compounds, Smoking cessation, Triazoles, All stub articles, Nervous ...

https://en.wikipedia.org/wiki/JNJ-39393406

The role of acetylcholine at the nicotinic receptor is still under investigation. It is likely implicated in the reward/ ... "Alpha-7 Nicotinic Receptor Signaling Pathway Participates in the Neurogenesis Induced by ChAT-Positive Neurons in the ... Acetylcholine acts at two classes of receptors in the central nervous system - muscarinic and nicotinic - which are each ... which also binds to the nicotinic receptor. The muscarinic action of acetylcholine in the CNS is implicated in learning and ...

https://en.wikipedia.org/wiki/Choline_acetyltransferase

... an α7 Nicotinic Acetylcholine Receptor Agonist, as a Treatment for Cognitive Impairment in Schizophrenia". ... Hilt, D.; Meltzer, H.; Gawry, M.; Ward, S.; Dgetluck, N.; Bhuvaneswaran, C. (February 2008). "EVP-6124, an alpha-7 nicotinic ...

https://en.wikipedia.org/wiki/SCoRS

... s are paralytic chemical compounds that inhibit neuronal and muscle-type nicotinic acetylcholine receptors. Although ... Structural Determinants and Functional Properties to Distinguish Neuronal alpha7 from Muscle alpha1(2)betagammadelta nAChRs. ... Pinnatoxins E, F and G target multiple nicotinic receptor subtypes. J. Neurochem. 2015 Nov;135(3):479-91. Hellyer SD, Selwood ... E and F display a high-affinity antagonism for the neuronal α7 and muscle α12βϒδ nicotine acetylcholine receptors (nAChRs). The ...

https://en.wikipedia.org/wiki/Pinnatoxin

... a class of potent nicotinic acetylcholine receptor-ligands". The Journal of Organic Chemistry. 73 (9): 3497-507. doi:10.1021/ ... a novel alpha7 ligand, is prevented through angiotensin II activation of a tyrosine phosphatase". The Journal of Pharmacology ... is a drug developed by Targacept which acts as a partial agonist for the α7 subtype of neural nicotinic acetylcholine receptors ... Anabasine Romanelli MN, Gratteri P, Guandalini L, Martini E, Bonaccini C, Gualtieri F (June 2007). "Central nicotinic receptors ...

https://en.wikipedia.org/wiki/TC-1698

8, 1995 Auxiliary subunits assist AMPA-type glutamate receptors Science March, 3, 2006 Nicotinic acetylcholine receptor redux: ... glycosylation and endoplasmic reticulum chaperone pathways for Alpha-7 nicotinic receptor oligomerization and membrane ... accessories might enable drug discovery for previously intractable and medically-important nicotinic acetylcholine receptors ( ... sensory α6-containing receptors for chronic pain (Journal of Clinical Investigation, 2020) and cochlear α9α10 receptors for ...

https://en.wikipedia.org/wiki/David_S._Bredt

Sapronov NS, Fedotova YO, Kuznetsova NN (December 2006). "Antiamnestic effect of alpha7-nicotinic receptor agonist RJR-2403 in ... Li X, Eisenach JC (June 2002). "Nicotinic acetylcholine receptor regulation of spinal norepinephrine release". Anesthesiology. ... is a drug which acts as a partial agonist at neural nicotinic acetylcholine receptors. It is subtype-selective, binding ... and nicotinic acid content". {{cite journal}}: Cite journal requires ,journal= (help) v t e (CS1 errors: missing periodical, ...

https://en.wikipedia.org/wiki/Rivanicline

... [ ... Differential Signalling Induced by alpha7 Nicotinic Acetylcholine Receptors in Hippocampal Dentate Gyrus in Vitro and in Vivo. ... Abstract Differential Signalling Induced by alpha7 Nicotinic Acetylcholine Receptors in Hippocampal Dentate Gyrus in Vitro and ... Synopsis Differential Signalling Induced by alpha7 Nicotinic Acetylcholine Receptors in Hippocampal Dentate Gyrus in Vitro and ...

https://www.niehs.nih.gov/research/resources/articles_journals/recent/pdf_2021/differential_signalling_induced_by_alpha7_nicotinic_acetylcholine_receptors_in_hippocampal_dentate_gyrus_in_vitro_and_in_vivo_.cfm

... in the mammalian brain are the pentameric alpha7 nAChRs which consist of five alpha7 subunits, and each subunit provides an ... orthosteric low affinity binding site for its endogenous ligand, acetylcholine. Distribution and high lev … ... The most abundant homomeric nicotinic acetylcholine receptors (nAChRs) ... Targeting alpha7 nicotinic acetylcholine receptors in the treatment of schizophrenia Mihály Hajós et al. Curr Pharm Des. 2010. ...

https://pubmed.ncbi.nlm.nih.gov/19909231

We previously reported that alpha7 nicotinic acetylcholine receptor (nAChR) agonism produces efficacy in preclinical cognition ... Targeting the nicotinic alpha7 acetylcholine receptor to enhance cognition in disease. Wallace TL, Porter RH. Wallace TL, et al ... In vivo pharmacological characterization of a novel selective alpha7 neuronal nicotinic acetylcholine receptor agonist ABT-107 ... In vivo pharmacological characterization of a novel selective alpha7 neuronal nicotinic acetylcholine receptor agonist ABT-107 ...

https://www.ncbi.nlm.nih.gov/pubmed/?holding=alzped&term=20504913

In vivo pharmacological characterization of a novel selective alpha7 neuronal nicotinic acetylcholine receptor agonist ABT-107 ... The overarching aim of this study was to continue to test the therapeutic utility of the alpha-7 nAChR agonist, ABT-107, in the ... Together, these findings show that targeting alpha-7 nAChRs may have potential utility for symptomatic alleviation and slowing ... ABT-107 increased extracellular cortical acetylcholine in rats, whereas acute administration increased cortical extracellular ...

https://alzped.nia.nih.gov/node/4856/printable/print

Here we have investigated the specific role of alpha7 nicotinic receptors in the ventral tegmental area for the neurobiological ... Previous data show that nicotinic receptors in the ventral tegmental area are of importance for the nicotine withdrawal ... Nicotinic Agonists * Receptors, Nicotinic * alpha7 Nicotinic Acetylcholine Receptor * 3,4-Dihydroxyphenylacetic Acid ... Nicotine withdrawal in the rat: role of alpha7 nicotinic receptors in the ventral tegmental area Neuroreport. 1999 Mar 17;10(4 ...

https://pubmed.ncbi.nlm.nih.gov/10208533/?dopt=Abstract

Association with alpha7 nicotinic acetylcholine receptors.. Sekhon HS; Keller JA; Proskocil BJ; Martin EL; Spindel ER. Am J ... Expression of SLURP-1, an endogenous alpha7 nicotinic acetylcholine receptor allosteric ligand, in murine bronchial epithelial ... 8. Nicotinic acetylcholine receptor expression in human airway correlates with lung function.. Lam DC; Luo SY; Fu KH; Lui MM; ... 5. Expression of nicotinic acetylcholine receptor subunit genes in non-small-cell lung cancer reveals differences between ...

https://pubmedhh.nlm.nih.gov/biomarkers/search.php?id=15588326&mod=related&page=1&outid=&proj=

The α7 neuronal nicotinic acetylcholine receptors (α7nAChRs) are essential for anti-inflammatory responses. The human-specific ... Role of Alpha-7 Nicotinic Acetylcholine Receptor in Recovery from Spinal Cord Injury. awarded to RHL and NK by the Wings for ... The α7 neuronal nicotinic acetylcholine receptors (α7nAChRs) are essential for anti-inflammatory responses. The human-specific ... CHRFAM7A, a human-specific and partially duplicated α7-nicotinic acetylcholine receptor gene with the potential to specify a ...

https://pubmed.ncbi.nlm.nih.gov/33956875

These considerations suggest that acetylcholine signaling by cholinergic interneurons is consistent with point-to-point ... from which we estimate the temporospatial distribution of acetylcholine after release from a synaptic vesicle and from multiple ... indicate that the temporospatial distribution of acetylcholine is both short-range and short-lived, and dominated by diffusion ... transmission within a steep concentration gradient, marked by transient peaks of acetylcholine concentration adjacent to ...

https://www.mdpi.com/1420-3049/27/4/1202

SLURP-1 specifically interacts with the alpha7 (α7) subunit, which is a piece of some nAChRs. Nicotinic acetylcholine receptors ... Central role of alpha7 nicotinic receptor in differentiation of the stratified squamous epithelium. J Cell Biol. 2002 Oct 28; ... Laboratory studies show that SLURP-1 can bind to nicotinic acetylcholine receptors (nAChRs). ... Through its interaction with these receptors, SLURP-1 may be involved in skin growth and development. ...

https://medlineplus.gov/genetics/gene/slurp1/

Alpha7 nicotinic acetylcholine receptors targeted by cholinergic developmental neurotoxicants: nicotine and chlorpyrifos. Brain ... Consumption of a high-fat diet in adulthood ameliorates the effects of neonatal parathion exposure on acetylcholine systems in ... Neonatal exposure to low doses of diazinon: long-term effects on neural cell development and acetylcholine systems. Environ ... Diverse neurotoxicants converge on gene expression for neuropeptides and their receptors in an In vitro model of ...

https://tools.niehs.nih.gov/srp/people/details.cfm?Person_ID=5199

Effects of the alpha7 nicotinic acetylcholine receptor agonist GTS-21 on the innate immune response in humans. Shock 2011;36:5- ... The alpha7 nicotinic acetylcholine receptor as a pharmacological target for inflammation. Br J Pharmacol 2007;151:915-29. ... Selective alpha7 nicotinic acetylcholine receptor agonists worsen disease in experimental colitis. Br J Pharmacol 2010;160:322- ... Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 2003;421:384-8. ...

https://gut.bmj.com/content/62/8/1214

Wang, H, Yu, M, and Ochari, M. "Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation." ... They identiﬁed a link between the bodys innate immune response and the receptor that binds nerve growth factor to a cell. This ... Tracey and his colleagues at North Shore Long Island Jewish Research Institute recently identiﬁed the molecular receptor for ... Kevin Tracey, M.D., discovered that the neurotransmitter acetylcholine can inhibit acute inﬂammation by blocking the activation ...

https://www.dana.org/article/climb-aboard-neuroimmunology-is-leaving-the-station/

Nicotinic Acetylcholine Receptor alpha7 Receptor, alpha-Bungarotoxin alpha-Bungarotoxin Receptors alpha7nAChR nAChR alpha7 ... Receptors, Nicotinic [D12.776.543.750.720.360.550] * alpha7 Nicotinic Acetylcholine Receptor [D12.776.543.750.720.360.550.500] ... Receptors, Nicotinic [D12.776.543.750.130.687] * alpha7 Nicotinic Acetylcholine Receptor [D12.776.543.750.130.687.500] ... Receptors, Nicotinic [D12.776.157.530.400.400.100.500] * alpha7 Nicotinic Acetylcholine Receptor [D12.776.157.530.400.400. ...

https://meshb.nlm.nih.gov/record/ui?ui=D064569

Role of nicotinic acetylcholine receptors in alcohol and nicotine co-addiction. One of the most probable targets for alcohol ... Alcohol enhances alpha4/beta2 nAChR function, but inhibits the activity of alpha7 nAChRs in vitro. By potentiating or ... interact is nicotinic acetylcholine receptors (nAChRs). Several different types of nAChRs are involved in nicotine addiction. ... and acetylcholine. For example, drugs that block nAChRs reduce alcohol drinking suggesting that nicotines primary receptor ...

https://grants.nih.gov/grants/guide/pa-files/PA-13-193.html

Cyclophilin dependent mechanism for alpha7 neuronal nicotinic acetylcholine receptor maturation.. Helekar, S., Colquhoun, L., ... Peptidyl prolyl cis-trans isomerase activity of cyclophilin A in functional homo-oligomeric receptor expression. Helekar, S. & ...

https://scholars.houstonmethodist.org/en/persons/santosh-helekar/publications/

A drug that blocks the alpha7 nicotinic acetylcholine receptor may provide a new method for combating drug addiction relapse, ... Using Light To Activate Opioid Receptors and Relieve Pain. Researchers have successfully activated the brains opioid receptors ...

https://neurosciencenews.com/neuroscience-terms/morphine/page/2/?filtered=atoz

The alpha7 nicotinic acetylcholine receptor on fibroblast-like synoviocytes and in synovial tissue from rheumatoid arthritis ... Numerous innate immune sensing pathways are found in the joint-specifically, Toll-like receptors (TLRs), NOD-like receptors and ... 25 lipid sensing nuclear receptors26 and protease sensing receptor systems such as PAR2.27 Increasingly moreover, the signal ... Liver X receptor agonism promotes articular inflammation in murine collagen-induced arthritis. Arthritis Rheum 2009;60:2655-65. ...

https://ard.bmj.com/content/69/11/1898?ijkey=7cbd54ea79087f8c93bff0d5059b643245705469&keytype2=tf_ipsecsha

D3.633.100.150.909.750.249 alpha7 Nicotinic Acetylcholine Receptor D12.776.543.550.425.500.100.500.500 D12.776.543.550.450.500. ... Receptors, Neurotensin D12.776.543.750.100.550 D12.776.543.750.695.550 Receptors, Nicotinic D12.776.543.550.425.500.100.500 ... Receptor Aggregation G4.299.780 G4.774 Receptor Cross-Talk G4.299.785 G4.794 Receptor Protein-Tyrosine Kinases D12.776.543.750. ... 60 D12.776.543.750.630 Receptor Tyrosine Kinase-like Orphan Receptors D12.776.543.750.60.233 D12.776.543.750.630.233 Receptor, ...

https://decs.bvs.br/E/mnchg2017.txt

... studying the therapeutic role of the alpha-7 nicotinic acetylcholine receptor against HIV-associated neurocognitive disorders ( ... Her dissertation work focuses on the role of auxiliary subunits in the regulation of AMPA receptor biogenesis. Her passion for ... His thesis was aimed to understand the role of the cannabinoid receptor type 2 activation in cathepsin B neurotoxicity promoted ... He is investigating the functional and structural effects that trans-synaptic interactions have on the kainate receptor, a ...

https://neuroscienceblueprint.nih.gov/training/d-span-award-f99k00/d-span-awardees

alpha7 Nicotinic Acetylcholine Receptor Entry term(s). Nicotinic Acetylcholine Receptor alpha7 Subunit, nAChR alpha7 alpha7 ... Nicotinic Acetylcholine Receptor alpha7. Receptor, alpha Bungarotoxin. Receptor, alpha-Bungarotoxin. Receptors, alpha- ... alpha7 Nicotinic Acetylcholine Receptor - Preferred Concept UI. M0089028. Scope note. A member of the NICOTINIC ACETYLCHOLINE ... Subunit, nAChR alpha7. alpha Bungarotoxin Receptors. alpha-Bungarotoxin Receptor. alpha-Bungarotoxin Receptors. alpha7 Subunit ...

https://decs.bvsalud.org/en/ths/resource/?id=55319

https://meshb-prev.nlm.nih.gov/record/ui?ui=D064569

The distribution of the alpha7 nicotinic acetylcholine receptor in healthy aging: An in vivo positron emission tomography study ... PET imaging of α,sub,7,/sub, nicotinic acetylcholine receptors: a comparative study of [,sup,18,/sup,F]ASEM and [,sup,18,/ ... Development of ,sup,11,/sup,C-Labeled ASEM Analogues for the Detection of Neuronal Nicotinic Acetylcholine Receptors (α7- ... PET imaging evaluation of [(18)F]DBT-10, a novel radioligand specific to α7 nicotinic acetylcholine receptors, in nonhuman ...

https://pesquisa.bvsalud.org/perinatal/related/es/mdl-28993233

... , Kawai ... BDNF up-regulates alpha7 nicotinic acetylcholine receptor levels on subpopulations of hippocampal interneurons. Author(s): ... Nicotinic acetylcholine receptors containing the alpha7 gene product are expressed at substantial levels in the hippocampus. ... Cellular distribution of the nicotinic acetylcholine receptor alpha7 subunit in rat hippocampus. Author(s): Mielke JG, Mealing ...

https://www.indexindex.com/journal-of-neuroscience-and-neuropharmacology/nicotinic-alpha-receptor-clusters-on-hippocampal-gabaergic-neurons-regulation-by-synaptic-activity-and-neurotrophins-596623.html

Nicotine causes nephrotoxicity through the induction of nlrp6 inflammasome and alpha7 nicotinic acetylcholine receptor. Zheng, ... Peroxisomal proliferator-activated receptor-α protects renal tubular cells from doxorubicin-induced apoptosis. Lin, H., Hou, C ... Peroxisome proliferator-activated receptor alpha plays a crucial role in l-carnitine anti-apoptosis effect in renal tubular ... Peroxisome proliferator-activated receptor α protects renal tubular cells from gentamicin-induced apoptosis via upregulating Na ...

https://hub.tmu.edu.tw/en/persons/yung-ho-hsu/publications/?type=%2Fdk%2Fatira%2Fpure%2Fresearchoutput%2Fresearchoutputtypes%2Fcontributiontojournal%2Farticle&ordering=title&descending=true

Synuclein N0000011305 alpha-Tocopherol N0000179281 alpha-Tocopherol Acetate N0000189396 alpha7 Nicotinic Acetylcholine Receptor ... Nicotinic N0000178729 Receptors, NK Cell Lectin-Like N0000169896 Receptors, Notch N0000168947 Receptors, Odorant N0000175301 ... Type 3 N0000168822 Receptor, IGF Type 1 N0000168823 Receptor, IGF Type 2 N0000168857 Receptor, Insulin N0000175243 Receptor, ... 5-HT2B N0000168886 Receptor, Serotonin, 5-HT2C N0000168812 Receptor, TIE-1 N0000168813 Receptor, TIE-2 N0000168854 Receptor, ...

https://evs.nci.nih.gov/ftp1/FDA/ndfrt/Archive/StructuralClass%202015-10-05.txt

... suggest that a receptor for amyloid beta peptide on the cell surface of neurons is the alpha7 nicotinic acetylcholine receptor ... Sweatt will use genetic approaches to examine whether deletion of the alpha7 receptor gene leads to amelioration of memory ... The identification of the alpha 7 receptor involvement in AD allows for the future study of agents that block the receptor as ...

https://www.brightfocus.org/grant/alpha7-nicotinic-receptors-and-map-kinase-ad-models

... both inhibit human recombinant alpha7 and alpha4beta2 neuronal nicotinic acetylcholine receptors in Xenopus oocytes. (1/27). 1 ... the preservative BCl and the Ketalar mixture on human neuronal nicotinic acetylcholine receptors (nAChRs) composed of the ... 2. Ketamine inhibited responses to 1 mM acetylcholine (ACh) in both the human alpha7 and alpha4beta2 nAChRs, with IC(50) values ... 4. Since alpha7 nAChRs are likely to be inhibited during clinical use of Ketalar, the actions of ketamine and BCl on this ...

https://lookformedical.com/en/search/benzethonium

Animal models of cognitive dysfunction relevant to both disorders suggest the α7 nicotinic acetylcholine receptor (nAChR) may ... Alpha-7 nicotinic agonists for cognitive deficits in neuropsychiatric disorders: A translational meta-analysis of rodent and ... Alpha-7 nicotinic agonists for cognitive deficits in neuropsychiatric disorders: A translational meta-analysis of rodent and ...

https://www.vumc.org/lewis-lab/publication/alpha-7-nicotinic-agonists-cognitive-deficits-neuropsychiatric-disorders-translational

The most abundant homomeric nicotinic acetylcholine receptors (nAChRs) in the mammalian brain are the pentameric alpha7 nAChRs which consist of five alpha7 subunits, and each subunit provides an orthosteric low affinity binding site for its endogenous ligand, acetylcholine. (nih.gov)
Since genetic linkage studies implicated the alpha7 nAChRs subunit gene CHRNA7 in schizophrenia, there is a considerable interest for developing drug therapies targeting alpha7 nAChRs. (nih.gov)
5. Expression of nicotinic acetylcholine receptor subunit genes in non-small-cell lung cancer reveals differences between smokers and nonsmokers. (nih.gov)
SLURP-1 specifically interacts with the alpha7 (α7) subunit, which is a piece of some nAChRs. (medlineplus.gov)
We have studied the effects of pure racemic ketamine, the preservative BCl and the Ketalar mixture on human neuronal nicotinic acetylcholine receptors (nAChRs) composed of the alpha7 subunit or alpha4 and beta2 subunits expressed in Xenopus laevis oocytes. (lookformedical.com)
Association between a genetic variant of the alpha-7 nicotinic acetylcholine receptor subunit and four types of dementia. (cdc.gov)

We previously reported that alpha7 nicotinic acetylcholine receptor (nAChR) agonism produces efficacy in preclinical cognition models correlating with activation of cognitive and neuroprotective signaling pathways associated with Alzheimer's disease (AD) pathology. (nih.gov)
In the present studies, the selective and potent alpha7 nAChR agonist 5-(6-[(3R)-1-azabicyclo[2.2.2]oct-3-yloxy] pyridazin-3-yl)-1H-indole (ABT-107) was evaluated in behavioral assays representing distinct cognitive domains. (nih.gov)
Studies were also conducted to address potential issues that may be associated with the clinical development of an alpha7 nAChR agonist. (nih.gov)
Inhibition of the alpha7 nAChRs occurred within a clinically relevant concentration range, while inhibition of the alpha4beta2 nAChR was observed only at higher concentrations. (lookformedical.com)
3. Ketamine is a noncompetitive inhibitor at both the alpha7 and alpha4beta2 nAChR. (lookformedical.com)
In contrast, BCl causes a parallel shift in the ACh dose-response curve at the alpha7 nAChR suggesting competitive inhibition. (lookformedical.com)
Animal models of cognitive dysfunction relevant to both disorders suggest the α7 nicotinic acetylcholine receptor (nAChR) may be a promising drug development target, with multiple clinical trials subsequently testing this hypothesis in individuals with SCZ and AD. (vumc.org)
In brain slices, alpha7 nAChR activation increased levels of the signaling molecules Ca2+ and cAMP in granule cells but not in GABAergic neurons. (nih.gov)
Taken together, the results shed new light on the action of alpha7 nAChR on brain circuitry. (nih.gov)

Distribution and high level expression of alpha7 nAChRs within the limbic circuitry, including the hippocampus and prefrontal cortical areas are in line with their involvement in various cognitive functions. (nih.gov)
Activation of alpha7 nAChRs generates a conformational change of sub-unit proteins, making the channel permeable to cations, in particular calcium, leading to change in neuronal activity and excitability, and via increased intracellular calcium, modulating transmitter release and neuronal network activity. (nih.gov)
In this review recent development of selective agonists and positive allosteric modulators of alpha7 nAChRs are discussed. (nih.gov)
In addition to summarizing medicinal chemistry efforts, both cellular and neuronal network pharmacology of alpha7 nAChRs are covered. (nih.gov)
The association between CHRNA7 gene and impaired P50 auditory gating has provided an attractive endophenotype, and its use as a potential translational biomarker for alpha7 nAChRs drug discovery is discussed. (nih.gov)
Laboratory studies show that SLURP-1 can bind to nicotinic acetylcholine receptors (nAChRs). (medlineplus.gov)
2. Ketamine inhibited responses to 1 mM acetylcholine (ACh) in both the human alpha7 and alpha4beta2 nAChRs, with IC(50) values of 20 and 50 microM respectively. (lookformedical.com)
The surprising increased inhibitory potency of Ketalar compared with pure ketamine appeared to be due to the activity of BCl, which inhibited both alpha7 (IC(50) value of 122 nM) and alpha4beta2 (IC(50) value of 49 nM) nAChRs at concentrations present in the clinical formulation of Ketalar. (lookformedical.com)
4. Since alpha7 nAChRs are likely to be inhibited during clinical use of Ketalar, the actions of ketamine and BCl on this receptor subtype may play a role in the profound analgesia, amnesia, immobility and/or autonomic modulation produced by this anaesthetic. (lookformedical.com)
the function may involve the proposed role as modulator of nicotinic acetylcholine receptors (nAChRs) activity. (nih.gov)
Activation of alpha7 nicotinic acetylcholine receptors (nAChRs) has distinct effects on the responses of different types of neurons in a brain region called the hippocampus, according to NIEHS researchers and their collaborators. (nih.gov)
Stimulation of alpha7 nAChRs enhances learning and memory and promotes the maturation of adult-born neurons. (nih.gov)
Specifically, it has not been clear whether alpha7 nAChRs mobilize different signaling pathways in distinct neuronal populations. (nih.gov)
To address this question, the researchers studied how stimulation of alpha7 nAChRs affects the responses of granule cells and GABAergic neurons in the hippocampus, which plays a critical role in learning and memory. (nih.gov)

HN - 2014 FX - Transplantation, Homologous MH - alpha7 Nicotinic Acetylcholine Receptor UI - D064569 MN - D12.776.157.530.400.400.100.500.500 MN - D12.776.543.550.425.500.100.500.500 MN - D12.776.543.585.400.500.100.500.500 MN - D12.776.543.750.51.687.500 MN - D12.776.543.750.720.360.550.500 MS - A member of the NICOTINIC ACETYLCHOLINE RECEPTOR subfamily of the LIGAND-GATED ION CHANNEL family. (nih.gov)

and AQW051, a Phase II alpha-7 nicotinic acetylcholine receptor partial agonist. (broadstreetalerts.com)

Genetic Association Study of the Alpha 7 Nicotinic Receptor (CHRNA7) with the Development of Schizophrenia and Bipolar Disorder in Korean Population. (cdc.gov)

Alpha-7 nicotinic agonists for cognitive deficits in neuropsychiatric disorders: A translational meta-analysis of rodent and human studies. (vumc.org)

Bilateral intrategmental injections of the selective alpha7 nicotinic receptor antagonist methyllycaconitine reduced locomotion in the nicotine-treated rats, but not in control animals. (nih.gov)
Peng C, Han Y, Sanders T, Chew G, Liu J, Hawrot E, Chi C, Wang C. "alpha4/7-conotoxin Lp1.1 is a novel antagonist of neuronal nicotinic acetylcholine receptors. (brown.edu)

Like other Ly6/uPAR-related proteins, SLURP-1 folds into a particular shape and is thought to attach (bind) to other proteins called receptors to carry out signaling within cells. (medlineplus.gov)
Proteomic Investigation of Murine Neuronal α7-Nicotinic Acetylcholine Receptor Interacting Proteins. (brown.edu)
Hawrot E. "Connecting the dots between G proteins, G protein coupled receptors, and neuronal nicotinic acetylcholine receptors (Comment on DOI 10.1002/bies.201300082). (brown.edu)

9. The expression and pharmacological characterization of nicotinic acetylcholine receptor subunits in HBE16 airway epithelial cells. (nih.gov)

Moreover, treatments targeting these receptors improve cognitive deficits associated with Alzheimer's disease, schizophrenia, and Down's syndrome. (nih.gov)

17. Nicotinic Receptor Subunits Atlas in the Adult Human Lung. (nih.gov)

We have used fluorescently labeled alpha-bungarotoxin to image alpha7-containing receptors on hippocampal neurons and to examine their regulation in culture. (indexindex.com)
A 3 d blockade of electrical activity with tetrodotoxin or NMDA receptors with APV dramatically reduced the proportion of GABAergic neurons expressing high levels of receptor staining and reduced the mean number of distinguishable receptor clusters on individual neurons. (indexindex.com)
Anti-BDNF and anti-NGF antibodies produced decrements equivalent to those of tetrodotoxin and APV, whereas addition of BDNF and NGF each increased staining levels and increased the number of distinguishable receptor clusters on GABAergic neurons. (indexindex.com)
The results indicate that both NMDA receptor activation and the neurotrophins BDNF and NGF are necessary to sustain the distribution patterns of alpha7-containing nicotinic receptors on GABAergic hippocampal neurons. (indexindex.com)
Preliminary results suggest that a receptor for amyloid beta peptide on the cell surface of neurons is the alpha7 nicotinic acetylcholine receptor. (brightfocus.org)
Similarly, recordings in mice revealed that nicotine injection increased alpha7 receptor-dependent activity of granule cells but did not increase the firing rate of GABAergic neurons. (nih.gov)

Paulo JA, Hawrot E. "Effect of homologous serotonin receptor loop substitutions on the heterologous expression in Pichia of a chimeric acetylcholine-binding protein with alpha-bungarotoxin-binding activity. (brown.edu)
Caffery PM, Krishnaswamy A, Sanders T, Liu J, Hartlaub H, Klysik J, Cooper E, Hawrot E. "Engineering neuronal nicotinic acetylcholine receptors with functional sensitivity to alpha-bungarotoxin: a novel alpha3-knock-in mouse. (brown.edu)

6. The ly-6 protein, lynx1, is an endogenous inhibitor of nicotinic signaling in airway epithelium. (nih.gov)
18. Expression of SLURP-1, an endogenous alpha7 nicotinic acetylcholine receptor allosteric ligand, in murine bronchial epithelial cells. (nih.gov)

Dr. Sweatt will use genetic approaches to examine whether deletion of the alpha7 receptor gene leads to amelioration of memory deficits exhibited in transgenic mice with AD and decreases in biochemical markers. (brightfocus.org)

Mulcahy MJ, Blattman SB, Barrantes FJ, Lukas RJ, Hawrot E. "Resistance to Inhibitors of Cholinesterase 3 (Ric-3) Expression Promotes Selective Protein Associations with the Human α7-Nicotinic Acetylcholine Receptor Interactome. (brown.edu)

10. Functional properties of homomeric, human alpha 7-nicotinic acetylcholine receptors heterologously expressed in the SH-EP1 human epithelial cell line. (nih.gov)

Previous data show that nicotinic receptors in the ventral tegmental area are of importance for the nicotine withdrawal syndrome. (nih.gov)
Here we have investigated the specific role of alpha7 nicotinic receptors in the ventral tegmental area for the neurobiological and behavioral consequences of nicotine withdrawal. (nih.gov)
Our results indicate that alpha7 nicotinic receptors in the ventral tegmental area are involved in the nicotine withdrawal syndrome. (nih.gov)
1. Nicotine signals through muscle-type and neuronal nicotinic acetylcholine receptors in both human bronchial epithelial cells and airway fibroblasts. (nih.gov)
2. Nicotine activates cell-signaling pathways through muscle-type and neuronal nicotinic acetylcholine receptors in non-small cell lung cancer cells. (nih.gov)
3. Nicotine enhances expression of the alpha 3, alpha 4, alpha 5, and alpha 7 nicotinic receptors modulating calcium metabolism and regulating adhesion and motility of respiratory epithelial cells. (nih.gov)
12. Nicotine induces fibrogenic changes in human liver via nicotinic acetylcholine receptors expressed on hepatic stellate cells. (nih.gov)
16. Effects of chronic nicotine treatment on expression of diverse nicotinic acetylcholine receptor subtypes. (nih.gov)
Blockade of either GABA(A) receptors with bicuculline or nicotinic receptors with d-tubocurarine had no effect, although exposure to nicotine could increase the level of receptor staining. (indexindex.com)

The cholinergic interneurons of the striatum account for a small fraction of all striatal cell types but due to their extensive axonal arborization give the striatum the highest content of acetylcholine of almost any nucleus in the brain. (mdpi.com)
Because of their specific locations and their high relative calcium permeability, the receptors not only mediate cholinergic transmission in the hippocampus but also influence signaling at noncholinergic synapses. (indexindex.com)
The aim of this study was to investigate the antiinflammatory benefits of SNS in colitis rats and explore the roles of the cholinergic antiinflammatory pathway, macrophage autophagy, and nucleotide oligomerization domain-like receptor thermal protein domain associated protein 3 (NLRP3) inflammatory bodies. (neuromodulationjournal.org)

11. Overexpression and activation of the alpha9-nicotinic receptor during tumorigenesis in human breast epithelial cells. (nih.gov)
The VN, through release of acetylcholine, dampens immune cell activation by interacting with α-7 nicotinic acetylcholine receptors. (bmj.com)
Many point to regulation of adaptive immunity, including ptpn22 (protein tyrosine phosphatase, non-receptor type 22 which regulates lymphocyte activation), ctla4 and cd40 (both implicated in co-stimulation of T cells). (bmj.com)

ABT-107 increased extracellular cortical acetylcholine in rats, whereas acute administration increased cortical extracellular signal-regulated kinase and cAMP response element- binding protein phosphorylation in mice, neurochemical and biochemical events germane to cognitive function. (nih.gov)

We review the evidence for this theory and use a mathematical model to integrate the measurements reported in the literature, from which we estimate the temporospatial distribution of acetylcholine after release from a synaptic vesicle and from multiple vesicles during tonic firing and pauses. (mdpi.com)

Ketamine and its preservative, benzethonium chloride, both inhibit human recombinant alpha7 and alpha4beta2 neuronal nicotinic acetylcholine receptors in Xenopus oocytes. (lookformedical.com)

The highest levels of staining for such receptors were most commonly found on GABAergic interneurons identified immunohistochemically. (indexindex.com)
The receptors were distributed in clusters on the soma and dendrites and were localized in part at GABAergic synapses. (indexindex.com)

Association study of the human partially duplicated alpha7 nicotinic acetylcholine receptor genetic variant with bipolar disorder. (cdc.gov)

2019. Perinatal diazinon exposure compromises the development of acetylcholine and serotonin systems. (nih.gov)

Central role of alpha7 nicotinic receptor in differentiation of the stratified squamous epithelium. (medlineplus.gov)

8. Nicotinic acetylcholine receptor expression in human airway correlates with lung function. (nih.gov)
13. Regulated expression of the IL-31 receptor in bronchial and alveolar epithelial cells, pulmonary fibroblasts, and pulmonary macrophages. (nih.gov)
14. Functional expression of alpha 7 nicotinic acetylcholine receptors in human periodontal ligament fibroblasts and rat periodontal tissues. (nih.gov)

As a past Established Investigator of the American Heart Association and Upjohn Professor of Pharmacology, my research interests include the understanding of the structure and function of nicotinic acetylcholine receptors and of the neurotoxins that target these important receptors. (brown.edu)

Proteomic investigation of human α7-nicotinic acetylcholine receptor signaling mechanisms. (brown.edu)

Nicotinic acetylcholine receptors containing the alpha7 gene product are expressed at substantial levels in the hippocampus. (indexindex.com)

Se compone en su totalidad de subunidades a7 pentaméricas expresadas en el sistema nervioso central, sistema nervioso autónomo, sistema vascular, linfocitos y bazo. (bvsalud.org)

Nicotinic acetylcholine receptors are best known for their role in chemical signaling between nerve cells, but they are also found in other tissues. (medlineplus.gov)
The function may implicate a possible role as a scavenger receptor for PLAU thereby blocking PLAU-dependent functions of PLAUR such as in cell migration and proliferation (PubMed:25168896). (nih.gov)

A drug that blocks the alpha7 nicotinic acetylcholine receptor may provide a new method for combating drug addiction relapse, researchers report. (neurosciencenews.com)
Researchers have successfully activated the brain's opioid receptors using optogenetics. (neurosciencenews.com)

The identification of the alpha 7 receptor involvement in AD allows for the future study of agents that block the receptor as potential therapeutics for AD. (brightfocus.org)

Association with alpha7 nicotinic acetylcholine receptors. (nih.gov)

Through its interaction with these receptors, SLURP-1 may be involved in skin growth and development. (medlineplus.gov)

Anatomy35

Organisms17

Diseases7

Chemicals and Drugs132

Analytical, Diagnostic and Therapeutic Techniques and Equipment18

Psychiatry and Psychology5

Phenomena and Processes42

Disciplines and Occupations3

Information Science3

Health Care1

Selective effects of a 4-oxystilbene derivative on wild and mutant neuronal chick alpha7 nicotinic receptor. (1/725)

Pairwise interactions between neuronal alpha7 acetylcholine receptors and alpha-conotoxin ImI. (2/725)

alpha-bungarotoxin receptors contain alpha7 subunits in two different disulfide-bonded conformations. (3/725)

Minimal conformation of the alpha-conotoxin ImI for the alpha7 neuronal nicotinic acetylcholine receptor recognition: correlated CD, NMR and binding studies. (4/725)

Alpha7 nicotinic receptor subunits are not necessary for hippocampal-dependent learning or sensorimotor gating: a behavioral characterization of Acra7-deficient mice. (5/725)

Cell-free expression and functional reconstitution of homo-oligomeric alpha7 nicotinic acetylcholine receptors into planar lipid bilayers. (6/725)

Strychnine activates neuronal alpha7 nicotinic receptors after mutations in the leucine ring and transmitter binding site domains. (7/725)

Nicotinic receptor activation in human cerebral cortical interneurons: a mechanism for inhibition and disinhibition of neuronal networks. (8/725)

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Receptors, Nicotinic

alpha7 Nicotinic Acetylcholine Receptor

Nicotinic Antagonists

Nicotinic Agonists

Acetylcholine

Torpedo

Bungarotoxins

Nicotine

Receptors, Cholinergic

Conotoxins

Aconitine

Azocines

Mecamylamine

Quinolizines

Dihydro-beta-Erythroidine

Bicyclo Compounds, Heterocyclic

Electric Organ

Cobra Neurotoxin Proteins

Cholinergic Agents

Tubocurarine

Xenopus laevis

Protein Subunits

Azetidines

Pyridines

Myasthenia Gravis

Dimethylphenylpiperazinium Iodide

Carbachol

Receptors, Muscarinic

Oocytes

Amphibian Venoms

Neurons

Neuromuscular Junction

Anabasine

Muscles

Dose-Response Relationship, Drug

Benzylidene Compounds

Patch-Clamp Techniques

Ganglionic Stimulants

Cholinergic Agonists

Molecular Sequence Data

Galantamine

Amino Acid Sequence

Binding Sites

Alkaloids

Azirines

Agrin

Ion Channels

Xenopus

Hexamethonium

Cholinergic Antagonists

Vesicular Acetylcholine Transport Proteins

Choline

Mollusk Venoms

Radioligand Assay

Electrophysiology

Drug Partial Agonism

Rats, Sprague-Dawley

Binding, Competitive

Ligands

Membrane Potentials

Ganglia, Parasympathetic

Conus Snail

Tobacco Use Disorder

Photoaffinity Labels

Cholinesterase Inhibitors

Kinetics

Protein Binding

Muscarinic Agonists

Ion Channel Gating

Quinoxalines

Motor Endplate

Proadifen

Synaptic Transmission

Receptor, Muscarinic M1

Nitro Compounds

Benzazepines

Receptor Aggregation

Receptors, Serotonin, 5-HT3

Macromolecular Substances

Muscarinic Antagonists