Receptors, Nicotinic: 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.alpha7 Nicotinic Acetylcholine Receptor: 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.Nicotinic Antagonists: 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.Nicotinic Agonists: 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.Acetylcholine: 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.Torpedo: A genus of the Torpedinidae family consisting of several species. Members of this family have powerful electric organs and are commonly called electric rays.Bungarotoxins: 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: 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.Receptors, Cholinergic: 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.Conotoxins: 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)Aconitine: 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.AzocinesMecamylamine: 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.QuinolizinesDihydro-beta-Erythroidine: 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.Bicyclo Compounds, Heterocyclic: 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)Electric Organ: 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)Cobra Neurotoxin Proteins: 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.Cholinergic Agents: 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.Tubocurarine: A neuromuscular blocker and active ingredient in CURARE; plant based alkaloid of Menispermaceae.Xenopus laevis: 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.Protein Subunits: 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.AzetidinesPyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Myasthenia Gravis: 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)Dimethylphenylpiperazinium Iodide: 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.Carbachol: A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS.Receptors, Muscarinic: 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.Oocytes: 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).Amphibian Venoms: 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.Neurons: 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.Neuromuscular Junction: The synapse between a neuron and a muscle.Anabasine: A piperidine botanical insecticide.Muscles: Contractile tissue that produces movement in animals.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Benzylidene Compounds: Compounds containing the PhCH= radical.Patch-Clamp Techniques: 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.Ganglionic Stimulants: 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.Cholinergic Agonists: Drugs that bind to and activate cholinergic receptors.Molecular Sequence Data: 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.Galantamine: 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.Amino Acid Sequence: 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.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Alkaloids: 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)Azirines: Unsaturated azacyclopropane compounds that are three-membered heterocycles of a nitrogen and two carbon atoms.Agrin: 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.Ion Channels: 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.Xenopus: An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.Hexamethonium: 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.Cholinergic Antagonists: Drugs that bind to but do not activate CHOLINERGIC RECEPTORS, thereby blocking the actions of ACETYLCHOLINE or cholinergic agonists.Vesicular Acetylcholine Transport Proteins: 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.Choline: 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.Mollusk Venoms: 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.Radioligand Assay: Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).Electrophysiology: 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 Partial Agonism: Drug agonism involving selective binding but reduced effect. This can result in some degree of DRUG ANTAGONISM.Rats, Sprague-Dawley: 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.Binding, Competitive: 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.Ligands: 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)Membrane Potentials: 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, Parasympathetic: 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.Conus Snail: 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 Use Disorder: Tobacco used to the detriment of a person's health or social functioning. Tobacco dependence is included.Photoaffinity Labels: 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.Cholinesterase Inhibitors: 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.Kinetics: The rate dynamics in chemical or physical systems.Protein Binding: 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.Muscarinic Agonists: 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.Ion Channel Gating: 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.QuinoxalinesMotor Endplate: 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.Proadifen: An inhibitor of drug metabolism and CYTOCHROME P-450 ENZYME SYSTEM activity.Synaptic Transmission: 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.Receptor, Muscarinic M1: 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.Nitro Compounds: Compounds having the nitro group, -NO2, attached to carbon. When attached to nitrogen they are nitramines and attached to oxygen they are NITRATES.Benzazepines: Compounds with BENZENE fused to AZEPINES.Receptor, Angiotensin, Type 1: An angiotensin receptor subtype that is expressed at high levels in a variety of adult tissues including the CARDIOVASCULAR SYSTEM, the KIDNEY, the ENDOCRINE SYSTEM and the NERVOUS SYSTEM. Activation of the type 1 angiotensin receptor causes VASOCONSTRICTION and sodium retention.Receptors, Serotonin, 5-HT3: 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.Macromolecular Substances: 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.Muscarinic Antagonists: 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, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Cells, Cultured: 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.Allosteric Regulation: 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.Bicyclo CompoundsMyasthenic Syndromes, Congenital: 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)Brain: 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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Receptor, Muscarinic M3: A subclass of muscarinic receptor that mediates cholinergic-induced contraction in a variety of SMOOTH MUSCLES.Receptor, Muscarinic M2: 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.Isoxazoles: 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.Synaptic Membranes: 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.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Structure-Activity Relationship: 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.Electrophorus: 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.Erabutoxins: 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.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.Calcium: 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.Decamethonium Compounds: Compounds that contain the decamethylenebis(trimethyl)ammonium radical. These compounds frequently act as neuromuscular depolarizing agents.Lobeline: 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.Azabicyclo Compounds: 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.Cobra Venoms: 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.Nootropic Agents: 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.Protein Conformation: 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).Atropine: An alkaloid, originally from Atropa belladonna, but found in other plants, mainly SOLANACEAE. Hyoscyamine is the 3(S)-endo isomer of atropine.Phencyclidine: 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.Muscle Denervation: The resection or removal of the innervation of a muscle or muscle tissue.Mice, Inbred C57BLQuaternary Ammonium Compounds: 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.Quinuclidinyl Benzilate: A high-affinity muscarinic antagonist commonly used as a tool in animal and tissue studies.Acetylcholinesterase: 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.QuinuclidinesPhysostigmine: 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.Elapidae: 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)Hippocampus: 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.Habenula: 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.Epilepsy, Frontal Lobe: 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)Morantel: Antinematodal agent used mainly for livestock.Transfection: 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.Lymnaea: A genus of dextrally coiled freshwater snails that includes some species of importance as intermediate hosts of parasitic flukes.Parasympathomimetics: 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.Dopamine: 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.Synaptosomes: 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.Chickens: 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.Mice, Knockout: 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.Protein Structure, Tertiary: 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.Snake Venoms: 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.Gallamine Triethiodide: 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)Curare: 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.Iodine Radioisotopes: Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes.N-Methylscopolamine: A muscarinic antagonist used to study binding characteristics of muscarinic cholinergic receptors.Synapses: 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.Reflex, Righting: The instinctive tendency (or ability) to assume a normal position of the body in space when it has been displaced.Levamisole: 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)Chick Embryo: 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.Superior Cervical Ganglion: The largest and uppermost of the paravertebral sympathetic ganglia.Paranasal Sinus Neoplasms: Tumors or cancer of the PARANASAL SINUSES.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Myasthenia Gravis, Autoimmune, Experimental: 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)Receptor, Muscarinic M4: 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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Choline O-Acetyltransferase: An enzyme that catalyzes the formation of acetylcholine from acetyl-CoA and choline. EC 2.3.1.6.TritiumElectric Stimulation: Use of electric potential or currents to elicit biological responses.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Mutation: 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.Ventral Tegmental Area: 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.Herpestidae: The family of agile, keen-sighted mongooses of Asia and Africa that feed on RODENTS and SNAKES.Chlorisondamine: 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.Chromaffin Cells: 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.Electrophysiological Processes: The functions and activities of living organisms or their parts involved in generating and responding to electrical charges .gamma-Aminobutyric Acid: The most common inhibitory neurotransmitter in the central nervous system.Iodine Isotopes: 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.Allosteric Site: 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.Muscle, Skeletal: 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.Substance Withdrawal Syndrome: 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.Rubidium Radioisotopes: Unstable isotopes of rubidium that decay or disintegrate emitting radiation. Rb atoms with atomic weights 79-84, and 86-95 are radioactive rubidium isotopes.Hexamethonium Compounds: Compounds containing the hexamethylenebis(trimethylammonium) cation. Members of this group frequently act as antihypertensive agents and selective ganglionic blocking agents.Oxotremorine: A non-hydrolyzed muscarinic agonist used as a research tool.Snakes: Limbless REPTILES of the suborder Serpentes.Pyrantel: 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)Cholinergic Fibers: Nerve fibers liberating acetylcholine at the synapse after an impulse.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Animals, Newborn: Refers to animals in the period of time just after birth.RNA, Messenger: 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.Signal Transduction: 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.Phenylurea Compounds: Compounds that include the amino-N-phenylamide structure.Protein Structure, Secondary: 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.Gene Expression Regulation: 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.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Behavior, Animal: The observable response an animal makes to any situation.Nerve Tissue ProteinsStereoisomerism: 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)Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Parasympathetic Nervous System: 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.Corpus Striatum: 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.Interneurons: 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.Neuromuscular Blocking Agents: 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.Tetrodotoxin: 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.Molecular Structure: 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.Tectum Mesencephali: 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.Bupropion: 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.Cloning, Molecular: 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.PC12 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 Fusion Proteins: 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.Affinity Labels: 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.Neurotransmitter Agents: 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.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Tropanes: N-methyl-8-azabicyclo[3.2.1]octanes best known for the ones found in PLANTS.Presynaptic Terminals: 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.Autoradiography: 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)Ganglia, Autonomic: 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.alpha 1-Antitrypsin: Plasma glycoprotein member of the serpin superfamily which inhibits TRYPSIN; NEUTROPHIL ELASTASE; and other PROTEOLYTIC ENZYMES.Electric Conductivity: The ability of a substrate to allow the passage of ELECTRONS.Etomidate: Imidazole derivative anesthetic and hypnotic with little effect on blood gases, ventilation, or the cardiovascular system. It has been proposed as an induction anesthetic.Radiochemistry: The study of the chemical and physical phenomena of radioactive substances.Primary Dysautonomias: 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.Muscle Proteins: The protein constituents of muscle, the major ones being ACTINS and MYOSINS. More than a dozen accessory proteins exist including TROPONIN; TROPOMYOSIN; and DYSTROPHIN.Snails: Marine, freshwater, or terrestrial mollusks of the class Gastropoda. Most have an enclosing spiral shell, and several genera harbor parasites pathogenic to man.Insecticides: 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.Receptor, Muscarinic M5: 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.

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)

*Nicotinic agonist

Nicotinic Alpha7 Acetylcholine Receptor Agonist Program Rollema, H.; Chambers, L.K; Coe, J.W.; Glowa, J.; Hurst, R.S.; Lebel, L ... Agonist 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 ... The development of nicotinic acetylcholine receptor agonists has come a long way since then. The nicotinic acetylcholine ...

*Endophenotype

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

*PNU-120,596

"Alpha7 and non-alpha7 nicotinic acetylcholine receptors modulate dopamine release in vitro and in vivo in the rat prefrontal ... Young, G.; Zwart, R.; Walker, A.; Sher, E.; Millar, N. (2008). "Potentiation of alpha7 nicotinic acetylcholine receptors via an ... "A novel positive allosteric modulator of the alpha7 neuronal nicotinic acetylcholine receptor: in vitro and in vivo ... Barron, S.; Mclaughlin, J.; See, J.; Richards, V.; Rosenberg, R. (2009). "An allosteric modulator of alpha7 nicotinic receptors ...

*CHRNA7

Alpha-7 nicotinic receptor Nicotinic acetylcholine receptor Acetylcholine receptor ENSG00000175344 GRCh38: Ensembl release 89: ... 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. ...

*Nicotinic acetylcholine receptor

Sadigh-Eteghad S, Mahmoudi J, Babri S, Talebi M (2015). "Effect of alpha-7 nicotinic acetylcholine receptor activation on beta- ... 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 ...

*Cobratoxin

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- ...

*PNU-282,987

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 ...

*Retinal regeneration

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

*Adult neurogenesis

"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 ...

*RIC3

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 ( ...

*CHRFAM7A

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 ...

*Brain-derived neurotrophic factor

"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. ...

*WAY-317,538

"Procognitive and neuroprotective activity of a novel alpha7 nicotinic acetylcholine receptor agonist for treatment of ... is a drug that acts as a potent and selective full agonist for the α7 subtype of neural nicotinic acetylcholine receptors. It ... Novel alpha 7 nicotinic acetylcholine receptor agonist". Bioorganic & Medicinal Chemistry. 17 (14): 5247-5258. doi:10.1016/j. ... but was selected for further development on the basis of its high selectivity over related receptors, ease of synthesis, and ...

*Memantine

Aracava Y, Pereira EF, Maelicke A, Albuquerque EX (March 2005). "Memantine blocks alpha7* nicotinic acetylcholine receptors ... Buisson B, Bertrand D (1 March 1998). "Open-channel blockers at the human alpha4beta2 neuronal nicotinic acetylcholine receptor ... Memantine acts as a non-competitive antagonist at different neuronal nicotinic acetylcholine receptors (nAChRs) at potencies ... It has been shown that the number of nicotinic receptors in the brain are reduced in Alzheimer's disease, even in the absence ...

*Alpha-7 nicotinic receptor

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 ... 2005). "A novel positive allosteric modulator of the alpha7 neuronal nicotinic acetylcholine receptor: in vitro and in vivo ... 2007). "An allosteric modulator of the alpha7 nicotinic acetylcholine receptor possessing cognition-enhancing properties in ...

*3-Bromocytisine

... alpha4beta2 and alpha4beta4 nicotinic acetylcholine receptors". Journal of Neurochemistry. 78 (5): 1029-1043. doi:10.1046/j. ... "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 ... "Increase in locomotor activity after acute administration of the nicotinic receptor agonist 3-bromocytisine in rats". European ...

*Mir-590 microRNA precursor family

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 ...

*Mecamylamine

... 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 ...

*PHA-543,613

... an agonist of the alpha7 nicotinic acetylcholine receptor, for the potential treatment of cognitive deficits in schizophrenia: ... is a drug that acts as a potent and selective agonist for the α7 subtype of neural nicotinic acetylcholine receptors, with a ...

*SB-206553

... 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. Forbes IT; Ham P; ... 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 ...

*Innate immune system

... the neurotransmitter that inhibits cytokine release by interacting with alpha7 nicotinic acetylcholine receptors (CHRNA7) ... Toll-like receptors are a major class of pattern recognition receptor, that exists in all coelomates (animals with a body- ... These cells present receptors contained on the surface or within the cell, named pattern recognition receptors (PRRs), which ... These proteins contain domains similar to the NOD Like Receptors and Toll-like receptors utilized in animal innate immunity. ...

*Gitte Moos Knudsen

"11C-NS14492 as a novel PET radioligand for imaging cerebral alpha7 nicotinic acetylcholine receptors: in vivo evaluation and ... "Mass dose effects and in vivo affinity in brain PET receptor studies-a study of cerebral 5-HT4 receptor binding with [11C] ... "Changes in 5-HT4 receptor and 5-HT transporter binding in olfactory bulbectomized and glucocorticoid receptor heterozygous mice ... Her interest in brain imaging has led to a deeper understanding of how many receptors act within the brain, and she has ...

*CHRNA5

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". Hogg RC, Raggenbass M, Bertrand D (2003). "Nicotinic acetylcholine receptors: from structure to brain ... 1997). "Comparative structure of human neuronal alpha 2-alpha 7 and beta 2-beta 4 nicotinic acetylcholine receptor subunits and ...

*5-HT2B receptor

... 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 ... Moreover, 5-HT2B receptors were recently shown to be overexpressed in human failing heart and antagonists of 5-HT2B receptors ... Research claims serotonin 5-HT2B receptors have effect on liver regeneration. 5-HT receptor GRCh38: Ensembl release 89: ...

*Inflammatory reflex

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

*Alpha-4 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; ... potent nicotinic acetylcholine receptor agonists". J. Med. Chem. 49 (26): 7843-53. doi:10.1021/jm060846z. PMID 17181167. Ji, ...
Dineley KT, Westerman M, Bui D, Bell K, Ashe KH, Sweatt JD. Beta-amyloid activates the mitogen-activated protein kinase cascade via hippocampal alpha7 nicotinic acetylcholine receptors: In vitro and in vivo mechanisms related to Alzheimers disease ...
The 16 nACh receptor subunits identified to date are defined using a Greek letter sometimes followed by an Arabic numeral (neither subscripted nor superscripted). For example, there are nine alpha subunits (α1-α9; α8 subunits have only been derived from chick), four beta subunits (β1-β4), and one each gamma (γ), delta (δ), and epsilon (ɛ) subunit. All nACh receptor α subunits share expression of a pair of tandem cysteine residues in the putative, N-terminal, extracellular region. These residues are near to a site on the α1, α4, or α7 subunits known to engage in agonist binding. None of the other subunits (i.e., β1-β4, γ, δ, or ɛ) have these tandem cysteines. Several approaches have been taken in attempts to illuminate relationships between nACh receptor subunits and their genes. At a low level of resolution, these analyses make it clear that same nACh receptor subunits and their genes are most closely related (e.g., the β1, γ, δ, and ɛ grouping; uniqueness of the α7/α8 ...
BioAssay record AID 356556 submitted by ChEMBL: Agonist activity at human nicotinic alpha3beta4 receptor expressed in human IMR32 cells at 50 uM by cell based membrane potential assay relative to (+/-)-epibatidine.
Background Non-coding single nucleotide polymorphisms within the nicotinic acetylcholine receptor alpha 4 subunit gene (CHRNA4) are robustly associated with various neurological and behavioral phenotypes including schizophrenia, cognition and smoking. The most commonly associated polymorphisms are located in exon 5 and segregate as part of a haplotype. So far it is unknown if this haplotype is indeed functional, or if the observed associations are an indirect effect caused by linkage disequilibrium with not yet identified adjacent functional variants. We therefore analyzed the functional relevance of the exon 5 haplotype alleles. Results Using voltage clamp experiments we were able to show that the CHRNA4 haplotype alleles differ with respect to their functional effects on receptor sensitivity including reversal of receptor sensitivity between low and high acetylcholine concentrations. The results indicate that underlying mechanisms might include differences in codon usage bias and changes in ...
BioAssay record AID 145983 submitted by ChEMBL: Binding affinity towards rat nicotinic acetylcholine receptor alpha2-beta2 expressed in HEK293 cells using [3H]EB as radioligand.
Buy our Human Nicotinic Acetylcholine Receptor alpha 7 peptide. Ab24285 is a blocking peptide for ab23832 and has been validated in BL. Abcam provides free…
Buy our Recombinant Human Nicotinic Acetylcholine Receptor alpha 1 protein. Ab114482 is a protein fragment produced in Wheat germ and has been validated in WB…
Nicotine is a chemical with multiple biological and neurological actions. It is a natural alkaloid that mimics the effects of acetylcholine as a neurotransmitter. Nicotinic acetylcholine receptors are cholinergic receptors that activate ligand-gated ion channels in the plasma membranes of certain neurons and muscle cells. These ion channels are opened by the binding of nicotine. Nicotinic acetylcholine receptors are the best-studied of the ionotropic receptors, being found throughout the nervous system and in the neuromuscular junctions of somatic muscles. When the channel opens, positively-charged sodium ions enter the cell and positively-charged potassium ions exit for a net positive increase inside the cell. Research suggests that nicotinic acetylcholine receptors may have a role in cognitive performance, as well as affecting mood, reducing pain sensitivity, and enhancing the release of other neurotransmitters. Sigma-Aldrich offers antibodies that have agonist and antagonist effects on nicotinic
Infants exposed to cigarette smoked during pregnancy into infancy have increased respiratory and cardiac abnormalities. Nicotine, the major neurotoxic component of cigarette smoke, induces its actions by binding to nicotinic acetylcholine receptors (nAChR), with one downstream effect being increased apoptosis. Using a pre- into post- natal cigarette smoke exposure mouse model (SE), we studied the immunohistochemical expression of nAChR subunits α2, α3, α4, α5, α7, α9, β1 and β2 and two markers of apoptosis, active caspase-3 and TUNEL, in seven nuclei of the medulla and facial nucleus of the pons in male mice. Pups of dams exposed to two cigarettes (nicotine ≤1.2mg, CO ≤15mg) twice daily for six weeks prior to mating, during gestation and lactation (n=5; SE), were compared to pups exposed to air under the same condition (n=5; SHAM) at P20. Results showed that the hypoglossal nucleus had increased α3, α4, α7, α9, Casp-3 and TUNEL, dorsal motor nucleus of the vagus had increased ...
RIC-3 (resistant to inhibitor of cholinesterase) is a transmembrane protein, found in invertebrates and vertebrates, that modulates the surface expression of a variety of nicotinic acetylcholine receptors (nAChRs) in neurons and other cells. To understand its mechanism of action, we have investigated the cellular location, transmembrane topology and roles of the functional domains of RIC-3 in facilitating α7 assembly and surface expression in cultured mammalian cells. We show that the mouse protein is targeted to the endoplasmic reticulum (ER) by the first 31 amino acids which act as a cleavable signal sequence. The mature protein is a single-pass type I transmembrane protein whose N-terminus resides in the lumen of the ER with the coiled-coil domain in the cytoplasm. Functional analysis shows that facilitation of surface expression of α7 in mammalian cells is reduced in mutants lacking the signal peptide, the lumenal segment and the coiled-coil domain, but not in those lacking the long ...
TY - JOUR. T1 - Adult forms of nicotinic acetylcholine receptors are expressed in the absence of nerve during differentiation of a mouse skeletal muscle cell line. AU - Shepherd, Dawn. AU - Brehm, Paul. PY - 1994. Y1 - 1994. N2 - Changes in the functional properties of acetylcholine receptor (AchR) channels were followed in the C2 muscle cell line over the period of 1 to 17 days following myotube formation. Up to 1 week after myotube formation, the predominant class of channel exhibited low (45 pS) conductance and long mean channel open time (14 msec), characteristic of the major type of AchR in embryonic skeletal muscle. Three additional Ach-activated currents with conductances lower than 45 pS and long channel open times were also observed. Seven to 10 days following myotube formation, channels of 45 pS and 65 pS and short (2-6 msec) mean open duration were observed, characteristic of receptor channels in adult muscle. Increases in ε subunit mRNA levels preceded the functional expression of ...
Molecular and cell biological characterisation of neuronal nicotinic acetylcholine receptors (nAChRs) provides an insight into their functional roles and potential as therapeutic targets for neurological disorders. Nicotinic receptors are oligomeric ligand-gated ion channels, comprising five subunits. Twelve vertebrate neuronal nAChR subunits (2-10 and 2-4) have been cloned to date, with considerable diversity observed in nAChR subunit composition. Heterologous expression of cloned subunits is a powerful method for investigating ion channel receptor pharmacology and subunit composition, but achieving efficient expression of some nAChRs in cultured cell lines has proved difficult. In this study, chimeras containing the N-terminal domain of the nAChR subunits, fused to the C-terminal region of the 5-hydroxtryptamine type 3 receptor subunit, 5HT3A, were constructed to overcome some of the challenges of recombinant nAChR expression. When combinations of wild-type and chimeric subunits were expressed ...
Neuronal nicotinic acetylcholine receptors (nAChRs) are excitatory ligand‐gated ion channels that perform important roles throughout the nervous systems of both vertebrate and invertebrate organisms. Impairments to human nAChRs and cholinergic transmission are thought to underlie the pathophysiologies of several neurological and psychological diseases including schizophrenia, Alzheimers disease, Parkinsons disease and certain forms of epilepsy. They are also the receptors that mediate the effects of tobacco smoking and contribute to the physiological and psychological changes associated with nicotine addiction. The aim of this thesis is to further our understanding of neuronal nAChRs from a pharmacological and molecular viewpoint. Research described in this thesis focuses on numerous aspects of neuronal nAChRs; allosteric modulators, insect nAChRs and chaperone proteins. Allosteric modulators of nAChRs are ligands that alter the receptors responsiveness to agonists via sites that are ...
Neuronal nicotinic acetylcholine receptors (nAChR) can modulate many cellular mechanisms, such as cell survival and memory processing, which are also influenced by the serine/ threonine protein kinases ERK1/2. In SH-SY5Y cells and hippocampal neurones, nicotine (100 mum) increased the activity of ERK1/2. This effect was Ca2+ dependent, and prevented by the alpha7 nAChR antagonist alpha-bungarotoxin (alpha-Bgt) and an inhibitor (PD98059) of the upstream kinase MEK. To determine the intervening steps linking Ca2+ entry to MEK-ERK1/2 activation, inhibitors of Ca2+-dependent kinases were deployed. In SH-SY5Y cells, selective blockers for PKC (Ro 31-8220), CaM kinase II (KN-62) or P13 kinase (LY 294002) failed to inhibit the nicotine-evoked increase in ERK1/2 activity. In contrast, two structurally different inhibitors of PKA (KT 5720 and H-89) completely prevented the nicotine-dependent increase in ERK1/2 activity. Inhibition of the nicotine-evoked increase in ERK1/2 activity by H-89 was also ...
Neuronal nicotinic acetylcholine receptors (nAChR) can regulate several neuronal processes through Ca2+-dependent mechanisms. The versatility of nAChR-mediated responses presumably reflects the spatial and temporal characteristics of local changes in intracellular Ca2+ arising from a variety of sources. The aim of this study was to analyse the components of nicotine-evoked Ca2+, signals in SH-SY5Y cells, by monitoring fluorescence changes in cells loaded with fluo-3 AM. Nicotine (30 muM) generated a rapid elevation in cytoplasmic Ca2+ that was partially and additively inhibited (40%) by alpha7 and alpha3beta2* nAChR subtype selective antagonists; alpha3beta4* nAChR probably account for the remaining response (60%). A substantial blockade (80%) by CdCl2 (100 muM) indicates that voltage-operated Ca2+ channels (VOCC) mediate most of the nicotine-evoked response, although the alpha7 selective antagonist alpha-bungarotoxin (40 nM) further decreased the CdCl2-resistant component. The elevation of ...
Urokinase plasminogen activator (uPA) contributes to atherosclerosis, restenosis and vascular remodeling. We have recently identified nAChRα1 as a functional cell receptor for uPA in addition to its classic receptor, uPAR. Here, we test the hypothesis that nAChRα1 plays a role in the pathogenesis of atherosclerosis. C57BL/6J ApoE−/− mice (male) were initially fed a Western diet for 8 wks. Plasmid DNA encoding scramble RNA (pScr) or siRNA (pSir2) for nAChRα1 was then injected into the mice (n=15) using an aortic hydrodynamic gene transfer protocol. Three mice from each group were sacrificed 7 days after DNA injection to confirm the nAChRα1 gene silencing. The rest of the mice continued on the Western diet for an additional 16 wks. Aortas were harvested for paraffin-embedding (aorta root), protein (ascending aorta and aortic arch) and RNA (descending aorta) (n=8). Whole aortas were isolated for oil red staining in 4 mice of each group. The nAChRα1 was highly up-regulated in aortic ...
购买Nicotinic Acetylcholine Receptor beta兔多克隆抗体(ab66429),Nicotinic Acetylcholine Receptor beta抗体经WB,IHC-Fr验证,可与人样本反应。中国现货速达。
Citation: Green, B.T., Welch, K.D., Cook, D., Gardner, D.R. 2011. Potentiation of the actions of acetylcholine, epibatidine, and nicotine by methyllycaconitine at fetal muscle-type nicotinic acetylcholine receptors. European Journal of Pharmacology. 662(1-3):15-21. Interpretive Summary: Toxic alkaloids from larkspur species cause muscle weakness in cattle. One alkaloid in particular, MLA, is found in high concentrations in toxic larkspur. This alkaloid is a potent and selective blocker of neuronal nicotinic acetylcholine receptors. This study characterized the affects of the blocker MLA on the actions of three nicotinic acetylcholine receptor agonists. These effects were assessed by measuring changes in membrane potential sensing dye responses of TE-671 cells. Changes in cell membrane potential from the addition of agonists were measured as changes in fluorescence of a membrane potential-sensitive dye. MLA alone was without effect. MLA at low concentrations potentiated the response of TE-671 ...
Close The Infona portal uses cookies, i.e. strings of text saved by a browser on the users device. The portal can access those files and use them to remember the users data, such as their chosen settings (screen view, interface language, etc.), or their login data. By using the Infona portal the user accepts automatic saving and using this information for portal operation purposes. More information on the subject can be found in the Privacy Policy and Terms of Service. By closing this window the user confirms that they have read the information on cookie usage, and they accept the privacy policy and the way cookies are used by the portal. You can change the cookie settings in your browser. ...
ABSTRACT: Hepatic ischemia-reperfusion (I/R) injury contributes to hepatic dysfunction and failure after liver transplantation, major hepatic resection, trauma, and hypovolemic shock. Therefore, reducing I/R injury is an important goal to improve the
Close The Infona portal uses cookies, i.e. strings of text saved by a browser on the users device. The portal can access those files and use them to remember the users data, such as their chosen settings (screen view, interface language, etc.), or their login data. By using the Infona portal the user accepts automatic saving and using this information for portal operation purposes. More information on the subject can be found in the Privacy Policy and Terms of Service. By closing this window the user confirms that they have read the information on cookie usage, and they accept the privacy policy and the way cookies are used by the portal. You can change the cookie settings in your browser. ...
Our data illustrate that the α10 −/− phenotype is distinct from that observed in the α9−/− mouse line in terms of hair cell physiological function and synaptic structure. In addition, our data demonstrate that the residual functional α9 nAChRs expressed in α10 −/− mice are insufficient to drive normal OC efferent function. Thus, our data definitively establish the requirement for α10 subunits in forming biologically relevant hair cell nAChRs.. Homomeric α9 nAChRs reconstituted in Xenopus oocytes produce small ACh-evoked currents (25). The presence of small ACh-evoked currents in some α10 −/− OHCs suggests the continued expression of functional α9 receptors that likely consist of homomeric subunits. Lack of nicotine-induced activation in OHCs that are otherwise ACh-responsive is consistent with the presence of α9 homomeric receptors. Moreover, the fact that OHCs from α9−/− mice do not present ACh-evoked currents rules out the possibility that in the absence of ...
Tested Applications: Immunohistochemistry. Rat monoclonal Nicotinic Acetylcholine Receptor (alpha4 Subunit) monoclonal antibody. 100% Bioguaranteed
We have investigated the topology of the alpha and delta subunits of the nicotinic acetylcholine receptor (AChR) from mammalian muscle synthesized in an in vitro translation system supplemented with dog pancreatic microsomes. Fusion proteins were expressed in which a carboxy-terminal fragment of bovine prolactin was attached downstream of each of the major putative transmembrane domains, M1-M4 and MA, in the AChR subunits. The orientation of the prolactin domain relative to the microsomal membrane was then determined for each protein by a proteolysis protection assay. Since the prolactin domain contains no information which either directs or prevents its translocation, its transmembrane orientation depends solely on sequences within the AChR subunit portion of the fusion protein. When subunit-prolactin fusion proteins with the prolactin domain fused after either M2 or M4 were tested, prolactin-immunoreactive peptides that were larger than the prolactin domain itself were recovered. No ...
Nicotinic acetylcholine receptors have been pursued for decades as potential molecular targets to treat cognitive dysfunction in Alzheimers disease due to their demonstrated role in processes underlying cognition.
Correction: Activation of α-7 Nicotinic Acetylcholine Receptor Reduces Ischemic Stroke Injury through Reduction of Pro-Inflammatory Macrophages and Oxidative Stress. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Although a fair number of genes coding for neuronal nAChRs have already been identified it is clear that reconstitution experiments have failed to describe all the subtypes observed in native cells (Pugh et al., 1995; Sorenson and Gallagher, 1996; Cuevas and Berg, 1998). The sequencing of the full genome of the nematode Caenorhabditis elegans has revealed the existence of over 40 potential genes encoding nicotinic acetylcholine receptor subunits in this organism (Littleton and Ganetzky, 2000), whereas to date only 16 nAChR subunits have been cloned in vertebrates (Lindstrom, 1997). Thus, yet undiscovered subunit could account for the existence of novel receptor proteins. In this work, we present evidence for the existence of a new nAChR subtype that would be composed by the association of α9 with a novel α10-subunit.. When expressed in X. laevis oocytes, the human α9-subunit was able to form recombinant homomeric channels activated by acetylcholine with properties similar to those reported ...
rs1051730, also known as D398N, is a SNP in the nicotinic acetylcholine receptor alpha 3 subunit CHRNA3 gene. In two recent (2008) studies, together comprising over 6,000 lung cancer patients of European ancestry, the rs1051730(T) allele was very significantly associated with increased risk. Having one copy (i.e. being a rs1051730(C;T) genotype) increased risk for lung cancer about 1.3x, and having two copies (rs1051730(T;T) individuals) represented 1.8x increased risk. Up to 14% of lung cancer incidence may be attributable to this allele.[PMID 18385738, PMID 18385676] An independent study published at the same time concluded that (T) allele carriers for SNP rs1051730 are not at higher risk of becoming smokers compared to (C) carriers. However, if they do smoke, (T) carriers are quite likely to smoke more cigarettes than (C) carriers, and as an apparent consequence, they are at higher risk for lung cancer as reported in this and other studies. This study therefore links rs1051730 directly to ...
Nicotinic Acetylcholine R alpha 4/CHRNA4 Antibodies available through Novus Biologicals. Browse our Nicotinic Acetylcholine R alpha 4/CHRNA4 Antibody catalog backed by our Guarantee+.
Medical Xpress is a web-based medical and health news service that features the most comprehensive coverage in the fields of neuroscience, cardiology, cancer, HIV/AIDS, psychology, psychiatry, dentistry, genetics, diseases and conditions, medications and more.
Gentaur molecular products has all kinds of products like :search , Meridian Life Science \ Nicotinic alpha 7 Receptor \ A4A316H for more molecular products just contact us
Nicotinic Acetylcholine Receptor beta小鼠单克隆抗体[B3](ab11150)可与人样本反应并经WB, IP, IHC, Flow Cyt实验严格验证,被5篇文献引用。
Les Laboratoires Servier (Servier) in France is developing conformationally restricted acetylcholine analogues as potential agents for the treatment of
Dajas-Bailador FA, Lima PA, Wonnacott S. The alpha7 nicotinic acetylcholine receptor subtype mediates nicotine protection against NMDA excitotoxicity in primary hippocampal cultures through a Ca(2+) dependent mechanism ...
Tying up Nicotine: New Selective Competitive Antagonist of the Neuronal Nicotinic Acetylcholine Receptors. / Petersen, Ida Nymann; Crestey, François; Jensen, Anders A; Indurthi, Dinesh C; Pedersen, Henrik; Andreasen, Jesper T; Balle, Thomas; Kristensen, Jesper L.. In: A C S Medicinal Chemistry Letters, Vol. 6, No. 4, 09.04.2015, p. 472-475.. Publication: Research - peer-review › Journal article ...
Neurons, Prefrontal Cortex, Acetylcholine, Attention, Brain, Mice, Role, Acetylcholine Receptors, Adult, Play, Nicotinic Acetylcholine Receptors, 5-ht, 5-ht(1a) Receptor, Cell, Serotonin, Feedback, Nicotinic Receptor, Thalamus, Anxiety, Patients
Previously, we purified the predominant subtype of brain nicotinic acetylcholine receptor (AChR), analyzed its structure, and found that it was composed of two kinds of subunit, with sequences encoded by cDNAs termed alpha 4 and beta 2. Here we express these cDNAs from chicken brain in stably transfected fibroblasts. We demonstrate by synthesis that these cDNAs encode subunit polypeptides of the expected sizes, which coassemble to form receptor macromolecules having the same size as native AChRs. Additionally, we demonstrate that the expressed AChRs exhibit the ligand-binding pharmacology of native brain AChRs and function as acetylcholine-gated ion channels. ...
netic abnormalities lead to the over-production of amy- Conversely, it has been shown that smoking im- loid-b, which is the major protein component of senile proves arousal and attention, and memory. Nicotinic acetylcholine receptor stimulation might enhance the It is controversial whether smoking is associated with formation of memory (Potter et al. 1999) alongside its the incidence of AD. Some reports have indicated the protective effect against the development of AD (Kihara negative relationship between smoking and AD (Hillier et al. 1997, 1998, 2001, Shimohama et al. 1996). Sub- and Salib 1997, Lee 1994, van Duijn and Hofman cutaneous administration of nicotine significantly im- 1991). Van Duijn and Hofman (1991) reported that the risk of Alzheimers disease decreased with the increase Conners continuous performance test (CPT) (White in the daily number of cigarettes smoked before onset of and Levin 1999). It has been reported that a significant disease (relative risk 0.3 in those smoking ...
Bionomics is developing BNC 210, a specific antagonist of the alpha 7 nicotinic acetylcholine receptor, for the treatment of anxiety disorders and depression.
rat my1 protein: binds to a regulatory element in the nicotinic acetylcholine receptor delta-subunit genes promoter; amino acid sequence given in first source
Nach resezierenden Mageneingriffen, insbesondere nach totaler Gastrektomie (GX), entwickelt sich beim Menschen langfristig in bis zu 50% der Fälle eine sekundäre
Bundesanstalt für Arbeitsschutz und Arbeitsmedizin - Alle Publikationen der BAuA - übersichtlich aufgelistet nach Kategorien oder über die Volltextsuche.
Cso.23Nbo.09O3Wo.91 (1) hexagonal, P63/mcm (No. 193), a = 7.3998(2) Å, c = 7.5732(2) Å, V = 359.1 ų, Ζ = 6, wR(P) =0.062, R(P)=0.044,R(I)=0.023, R(F)=0.012, T= 293 K. Cs0.29Nb0.10O3W0.90 (2), hexagonal, P63/mcm (No ...
Kreativhaus.de ist ein Premium-Onlineshop mit einer großen Auswahl an exklusiven Einrichtungsgegenständen.. Jedes Produkt kann bequem nach Hause bestellt werden.. ...
Kreativhaus.de ist ein Premium-Onlineshop mit einer großen Auswahl an exklusiven Einrichtungsgegenständen.. Jedes Produkt kann bequem nach Hause bestellt werden.. ...
Die Entwicklung einer Pankreasfistel ist meistens die Folge chirurgischer Behandlungen einer Bauchspeicheldrüsenläsion, seltener erscheint sie spontan nach einer akuten Pankreatitis sowie als...
TY - JOUR. T1 - Luminal and non-luminal non-competitive inhibitor binding sites on the nicotinic acetylcholine receptor (Review). AU - Arias, Hugo R.. PY - 1996/1/1. Y1 - 1996/1/1. N2 - The nicotinic acetylcholine receptor presents two very well differentiated domains for ligand binding that account for different cholinergic properties. In the hydrophilic extracellular region of the a subunit exist the binding sites for agonists such as the neurotransmitter acetylcholine, which upon binding trigger the channel opening, and for competitive antagonists such as d-tubocurarine, which compete for the former inhibiting its pharmacological action. For non-competitive inhibitors, a population of low-affinity binding sites have been found at the lipid-protein interface of the nicotinic acetylcholine receptor. In addition, at the M2 transmembrane domain, several high-affinity binding sites have been found for non-competitive inhibitors such as chlorpromazine, triphenylmethylphosphonium, the local ...
It is well established that nicotinic receptors in the mammalian striatum are involved in modulation of the release of several neurotransmitters, including dopamine. In addition, nicotinic receptors with high affinity for agonists have generally been found to be reduced in the striatum in Parkinsons disease. In the present study antibodies have been used to examine which subunits contribute to the striatal nicotinic receptor loss in Parkinsons disease, and whether the reduction in [(3)H]nicotine binding correlates with synaptic loss. Autopsy tissue from the putamen of 12 Parkinsons disease cases and 12 age-matched control subjects was analysed by immunoblotting using antibodies against recombinant peptides specific for alpha3, alpha4, alpha7, beta2 and beta4 nicotinic acetylcholine receptor (nAChR) subunits and the synaptic marker synaptophysin, in conjunction with assessment of [(3)H]nicotine binding by autoradiography. The data indicate that there is no loss of alpha3, alpha4, alpha7 and beta2
TY - JOUR. T1 - Purification and characterization of a protein tyrosine phosphatase which dephosphorylates the nicotinic acetylcholine receptor. AU - Mei, Lin. AU - Huganir, Richard L.. PY - 1991/12/1. Y1 - 1991/12/1. N2 - The nicotinic acetylcholine receptor (nAChR) is phosphorylated to a high stoichiometry on tyrosine residues both in vitro and in vivo. Moreover, tyrosine phosphorylation has been shown to regulate the functional properties of the receptor. We report here the purification and characterization of a protein tyrosine phosphatase that dephosphorylates tyrosine-phosphorylated nAChR from Torpedo electroplax, a tissue highly enriched in the nAChR. The 32P-labeled tyrosine phosphorylated nAChR was used as a substrate to monitor the enzyme activity during purification. The protein tyrosine phosphatase activity was purified using three consecutive cation-exchange columns (phosphocellulose, S Sepharose Fast Flow, Bio-Rex 70), followed by two affinity matrices (p-aminobenzylphosphonic ...
Incorporation of the alpha 5 nicotinic acetylcholine receptor ( nAChR) subunit can greatly influence nAChR function without altering receptor number. Although few animal studies have assessed the role of the alpha 5 nAChR in nicotine-mediated behaviors, recent evidence suggests an association between polymorphisms in the alpha 5 nAChR gene and nicotine dependence phenotypes in humans. Thus, additional studies are imperative to elucidate the role and function of the alpha 5 nAChR subunit in nicotine dependence.
The conformation of the neurotransmitter acetylcholine bound to the fully functional nicotinic acetylcholine receptor embedded in its native membrane environment has been characterized by using frequency-selective recoupling solid-state NMR. Six dipolar couplings among five resolved (13)C-labeled atoms of acetylcholine were measured. Bound acetylcholine adopts a bent conformation characterized with a quaternary ammonium-to-carbonyl distance of 5.1 A. In this conformation, and with its orientation constrained to that previously determined by us, the acetylcholine could be docked satisfactorily in the agonist pocket of the agonist-bound, but not the agonist-free, crystal structure of a soluble acetylcholine-binding protein from Lymnaea stagnali. The quaternary ammonium group of the acetylcholine was determined to be within 3.9 A of five aromatic residues and its acetyl group close to residues C187/188 of the principle and residue L112 of the complementary subunit. The observed |C O chemical shift is
(E)-5-(Pyrimidin-5-yl)-1,2,3,4,7,8-hexahydroazocine (TC299423) is a novel agonist for nicotinic acetylcholine receptors (nAChRs). We examined its efficacy, affinity, and potency for α6β2* (α6β2-containing), α4β2*, and α3β4* nAChRs, using [125I]-epibatidine binding, whole-cell patch-clamp recordings, and synaptosomal 86Rb+ efflux, [3H]-dopamine release, and [3H]-acetylcholine release. TC299423 displayed an EC50 of 30 - 60 nM for α6β2* nAChRs in patch-clamp recordings and [3H]-dopamine release assays. Its potency for α6β2* in these assays was 2.5-fold greater than that for α4β2*, and much greater than that for α3β4*-mediated [3H]-acetylcholine release. We observed no major off-target binding on 70 diverse molecular targets. TC299423 was bioavailable after intraperitoneal or oral administration. Locomotor assays, measured with gain-of-function mutant α6 (α6L9ʹS) nAChR mice, show that TC299423 elicits α6β2* nAChR-mediated responses at low doses. Conditioned place preference (CPP)
Introduction: alpha 7 nicotinic acetylcholine receptors (nAChRs) play an important role in vagus nerve-based cholinergic anti-inflammatory effects. This study was designed to assess the role of alpha 7 nAChRs in dextran sodium sulfate (DSS)-induced colitis in male and female mouse. We first compared disease activity and pathogenesis of colitis in alpha 7 knockout and wild-type mice. We then evaluated the effect of several alpha 7 direct and indirect agonists on the severity of disease in the DSS-induced colitis.
Drugs. 2,3-Dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX) from Ascent Scientific (Weston-SuperMare, UK). Dihydro-β-erythroidine hydrobromide (DHβE), methyllycaconitine (MLA), and PNU-120596 were purchased from Tocris Bioscience (Bristol, UK). SB-206553, picrotoxin, atropine, (-)nicotine, and acetylcholine were purchased from Sigma Chemical (Poole, Dorset, UK).. Recombinant and Native Cell Lines. GH4C1 cells stably transfected with pCEP4/rat α7 nAChR (α7-nAChR-GH4C1) were used in this study and maintained in poly-d-lysine-coated flasks in F10 medium supplemented with 15% horse serum and 2.5% fetal bovine serum, 1% penicillin-streptomycin, and 200 mg/ml hygromycin B at 37°C in a humidified 5% CO2 incubator. The 5-HT3A receptor cDNA was cloned from human brain RNA, and the rat α7 nAChR was cloned from PC12 cells. Human SHSY5Y cells and TE671 endogenously expressing α3- and α1-containing receptors, respectively, were used.. Measurement of Intracellular Ca2+Using the ...
Ethylbenzene and para-xylene (p-xylene), but not the chemically closely related organic solvents ortho-xylene (o-xylene) and meta-xylene (m-xylene), are known to cause ototoxicity and irreversible hearing loss, though the underlying mechanisms are still unknown. In this study, effects of ethylbenzene and of p-, o-, and m-xylene on human heteromeric α9α10 nicotinic ... read more acetylcholine receptors (nAChRs) expressed in Xenopus oocytes were investigated using the two-electrode voltage clamp technique. ACh dose-dependently evoked an α9α10 nAChR-mediated ion current with an EC50 of 137 μM. When ACh is applied at a low concentration (10 μM), the nAChR-mediated ion current is inhibited by a low concentration (10 μM) of ethylbenzene and p-xylene, but not by the same concentration of the non-ototoxic solvents. At a high solvent concentration (300 μM), all solvents cause inhibition of the ion currents evoked by 10 μM ACh. Ion currents evoked by a near maximum-effective concentration ACh (1 ...
There are two main research projects in my laboratory funded by grants from the Canadian Institutes of Health Research (CIHR) and the Natural Sciences and Engineering Research Council of Canada (NSERC). Both involve the structural characterization of integral membrane proteins using biophysical methods.. The first is titled "Structure and function of the nicotinic acetylcholine receptor in its membrane environment". The nicotinic acetylcholine receptor (nAChR) is a neurotransmitter-gated ion channel found at synapses located in both the nervous system and at neuromuscular junctions. The nAChR (and other homologs) plays a central role in rapid communication in the brain. Factors that influence the efficacy of synaptic communication play an important role in higher brain functions, such as memory and learning, etc. Lipids are potent modulators of nAChR function. Increasing evidence suggests that lipids play an important role modulating nAChR function under both normal and pathological conditions. ...
Communication in the nervous system takes place at chemical and electrical synapses, where neurotransmitter-gated ion channels, such as the nicotinic acetylcholine (ACh) receptor, and gap junction channels control propagation of electrical signals from one cell to the next. Newly developed electron crystallographic methods have revealed the structures of these channels trapped in open as well as closed states, suggesting how they work. The ACh receptor has large vestibules extending from the membrane which shape the ACh-binding pockets and facilitate selective transport of cations across a narrow membranespanning pore. When ACh enters the pockets it triggers a concerted conformational change that opens the pore by destabilizing a gate in the middle of the membrane made by a ring of pore-lining α-helical segments. The alternative open configuration of pore-lining segments reshapes the lumen and creates new surfaces, allowing the ions to pass through. The gap junction channel uses a similar ...
5-iodo-3-(2(S)-azetidinylmethoxy)pyridine (5-iodo-A-85380) and labeled it with 125I and123I. Here we present the results of experiments characterizing this radioiodinated ligand in vitro. The affinity of 5-[125I]iodo-A-85380 for α4β2 nAChRs in rat and human brain is defined by K d values of 10 and 12 pM, respectively, similar to that of epibatidine (8 pM). In contrast to epibatidine, however, 5-iodo-A-85380 is more selective in binding to the α4β2 subtype than to other nAChR subtypes. In rat adrenal glands, 5-iodo-A-85380 binds to nAChRs containing α3 and β4 subunits with 1/1000th the affinity of epibatidine, and exhibits 1/60th and 1/190th the affinity of epibatidine at α7 and muscle-type nAChRs, respectively. Moreover, unlike epibatidine and cytisine, 5-[125I]iodo-A-85380 shows no binding in any brain regions in mice homozygous for a mutation in the β2 subunit of nAChRs. Binding of 5-[125I]iodo-A-85380 in rat brain is reversible, and is characterized by high specificity and a slow rate ...
The ability of alpha4beta2 nicotinic acetylcholine receptors to modulate dopaminergic (DA) cell activity in the ventral tegmental area (VTA) in rat midbrain slices was assessed using a selective alpha4beta2 receptor agonist, TC-2559 ((E)-N-methyl-4-[3-(5-ethoxypyridin)y1]-3-buten-1-amine). The selectivity of TC-2559 was characterized across 6 recombinant human nicotinic receptors (alpha4beta2, alpha2beta4, alpha4beta4, alpha3beta4, alpha3beta2 and alpha7) stably expressed in mammalian cell lines. Using a fluorescent imaging plate reader and fluo-3 to monitor changes in intracellular calcium, TC-2559 was found to be at least 69 fold more potent on alpha4beta2 than on other heteromeric subtypes, with an efficacy of 33%. No activity on the homomeric alpha7 subtype was detected. TC-2559 also showed selectivity for alpha4beta2 over the alpha4beta4 and alpha7 subtypes expressed in Xenopus oocytes. When bath applied to VTA slices, TC-2559 increased the firing of DA cells in a dose-dependent manner, in ...
A publication in Amino Acids by researchers from UPF, CRG and other centers provides the first in vivo evidence of the involvement of the CHRNA5/A3/B4 gene cluster in nicotine addiction. It happens through modifying the activity of brain regions responsible for the balance between the rewarding and the aversive properties of this drug. CHRNA5/A3/B4 codes…
The authors integrate behavioral, electrophysiological, anatomical, and genetic data to establish an essential role for the Dα7 nAChR in giant fiber-mediated escape inDrosophila.
A leading global provider in the supply of high quality chemical products and contract services to the pharmaceutical, agrochemical and biotechnology sectors together with related industries and applications.
1G2G: Minimal conformation of the alpha-conotoxin ImI for the alpha7 neuronal nicotinic acetylcholine receptor recognition: correlated CD, NMR and binding studies.
1KC4: NMR structural analysis of alpha-bungarotoxin and its complex with the principal alpha-neurotoxin-binding sequence on the alpha 7 subunit of a neuronal nicotinic acetylcholine receptor.
Wishka, D.; Walker, D.; Yates, K.; Reitz, S.; Jia, S.; Myers, J.; Olson, K.; Jacobsen, E.; Wolfe, M. (2006). "Discovery of N-(3R)-1-azabicyclo2.2.2oct-3-ylfuro2,3-cpyridine-5-carboxamide, an agonist of the alpha7 nicotinic acetylcholine receptor, for the potential treatment of cognitive deficits in schizophrenia: synthesis and structure--activity relationship". Journal of Medicinal Chemistry 49 (14): 4425-4436. PMID 16821801. doi:10.1021/jm0602413. ...
Ac-Choline Receptor Alpha1 (129-145) (Human, Bovine, Mouse, Rat), 10 mg. This fragment of a conserved sequence in nicotinic acetylcholine receptor activates T helper lymphocytes and induces the production of autoantibodies that cause electrophysiologic
Dynein mutation increased adipose stores in early symptomatic SOD1(G93A) mice. A- mRNA levels of alpha subunit of the nicotinic acetylcholine receptor (AchRα)
Azanorbornylpurine derivatives were prepared by Mitsunobu reaction of appropriate hydroxyazanorbornane derivative with 6-chloropurine or construction of purine base at azanorbornylamines. The prepared target compounds were evaluated for antiviral activity and effect on neuronal and muscle nicotinic acetylcholine receptors. (C) 2011 Published by Elsevier Ltd ...
mt) - Zwei Nach-schlä-ge hat Karl-Heinz Beck be-nö-tigt, um am Sams-tag-abend mit ins-ge-samt fünf Ham-mer-schlä-gen den Zapf-hahn in das Frei-bier-fass rein-zu-schla-gen und da-mit den 38. Teu-rin-ger Sonn-tag zu er-öff-nen. Für den Bür-ger-meis-ter war das nach 31 Jah-ren sein letz-tes Fass.. Bei an-ge-neh-men som-mer-li-chen Tem-pe-ra-tu-ren hat-te sich der St. Mar-tin-Platz mit mu-si-ka-li-scher Be-glei-tung der Teu-rin-ger Ju-gend-ka-pel-le nach und nach ge-füllt. Für gu-te Stim-mung sorg-te nach dem Be-grü-ßungs-trunk dann die Grup-pe „Cu-be"mit Mu-sik aus den 50er-Jah-ren bis hin zu ak-tu-el-len Hits aus der Schla-ger- und Pop-sze-ne.. Der Sonn-tag-mor-gen sah dann nach dem öku-me-ni-schen Got-tes-dienst in der St. Mar-tin-Kir-che trü-be aus, so-dass zum Früh-schop-pen-kon-zert der Trach-ten-ka-pel-le und der Ch-or-ge-mein-schaft die Son-nen- zu Re-gen-schir-men um-funk-tio-niert wer-den muss-ten. Die teil-neh-men-den Ver-ei-ne trös-te-ten die Be-su-cher über die-sen ...
Im Rahmen einer vergleichenden retrospektiven Analyse wurden die präoperativen und intraoperativen Einflussfaktoren auf den frühen und mittelfristigen postoperativen Verlauf nach Fontan-Operation untersucht und die Ergebnisse der totalen cavopulmonale Anastomose mit einem intraatrialen lateralen Tunnel (LTFO, n = 25) und mit einem extrakardialen Kunststoff-Konduit (ECFO, n = 25) gegenüber gestellt. Postoperativ wurde nach ECFO ein komplikationsärmerer früher Verlauf mit kürzerer maschineller Beatmung und signifikant geringerer Inzidenz für frühe und mittelfristige Arrhythmien als nach LTFO beobachtet. Im frühen postoperativen Verlauf waren die schnellste Extubation und Entlassung bei den ECFO-Patienten möglich, bei denen keine Kardioplegie verwendet wurde. Unabhängige Risikofaktoren nach multivariater Analyse waren die Dauer der Kardioplegie in Bezug zu den unmittelbaren postoperativen Komplikationen, eine LTFO - sowohl für Tachy- als auch für Bradyarrhythmien - und die Inzision in ...
Vergleichen Sie alle Ticket-Angebote nach Victoria. Buchen Sie einen KLM-Flug nach Victoria oder profitieren Sie von einem der Sonderangebote unserer Airline-Partner.
Strömungswiderstand des verbleibenden Nierenparenchyms und renale arteriovenöse Sauerstoffdifferenz wurden bei Hunden unmittelbar nach der einseitigen Nephrektomie sowie 5 Wochen nach dem Eingriff...
I started to try and break the 10 charset limit of PHP non-alpha after @InsertScript showed me that PHP Dev supports [] syntax for arrays. I wondered if it would be possible to break the limit within production PHP. At first I thought you could but then after some testing I found that there was no way to concat without "." and no way to call a string as a function without $ and =. However since I got into PHP Non-alpha again I thought why not try and improve it and make the code tweetable ...
Zu den urogenitalen Neoplasien mit Ausnahme der testikul ren Keimzelltumoren herrscht Unklarheit ber die Indikation, das Ausma und den prognostischen Nutzen einer Metastasenresektion nach medikament ser systemischer Therapie. Diese operative...
Gsellhofer, Brigitte; Montoya, Pedro; Müller, Achim; Piesbergen, Christoph und Schandry, Rainer (Oktober 1992): Zum Zusammenhang zwischen Streßbewältigung und Blutdruckreaktion. In: Zeitschrift für experimentelle und angewandte Psychologie, Vol. 38, Nr. 3: S. 419-433 [PDF, 1MB] ...
Hinweise auf toxische Nebenwirkungen von Perfluorhexyloktan nach An-wendung in vitreoretinaler Chirurgie sowie nach Inkubation mit humanem reti-nalem Pigmentepithel und humanem retinalen Pigmentepithel und humanem kornealen Endothel in vitro ...
Solltet Ihr die Homepages bestimmter Firmen im Internet suchen, dann schaut doch auch mal in unserer Link-Datenbank unter der Rubrik "Hersteller" nach ...
Background & Purpose: Stroke is an important risk factor and one of the most devastating complications for bone fracture. We showed previously that bone fracture at the acute stage of ischemic stroke worsens, and activation of α7 nicotinic acetylcholine receptor (α7 nAchR) improves stroke recovery through attenuation of inflammation. We hypothesized that activation of α7 nAchR also improves blood-brain barrier integrity.. Methods: Permanent distal middle cerebral artery occlusion (pMCAO) was performed on C57BL/6J mice followed by tibia fracture 1 day later. Mice were treated intra-peritoneally with 0.8 mg/kg PHA 568487 (PHA, α7 nAchR-specific agonist), 6 mg/kg methyllycaconitine (MLA, α7 nAchR antagonist), or saline 1 and 2 days after pMCAO. Brain water content was assessed by measuring the wet and dry weight 3 days after pMCAO. The expression of monoamine oxidase B (MAO-B) in astrocytes and tight junction proteins was quantified in the peri-infarct region using immunostained brain sections ...
Radiant insights, inc Neuronal Acetylcholine Receptor Subunit Alpha 7 (CHRNA7) - Pipeline Review, H2 2016, provides in depth analysis on Neuronal Acetylcholine Receptor Subunit Alpha 7 (CHRNA7) targeted pipeline therapeutics. The report provides comprehensive information on the Neuronal Acetylcholine Receptor Subunit Alpha 7 (CHRNA7) , targeted therapeutics, complete with analysis by indications, stage of development,…
Characterization of binding sites and agonist-induced desensitization of the nicotinic acetylcholine receptor in Torpedo electric organ. . Download books free in pdf. Online library with books, university works and thousands of documents available to read online and download.
1 mCi quantities of Levo-[ring-2, 5, 6-3H]-Norepinephrine are available for your research. Application of [3H]Norepinephrine can be found in: paroxetine binding to the rat transporter in vivo in neuropsychopharmacology; endobain E decreasing uptake in rat hypothalamus in life science research, nicotinic acetylcholine receptor-mediated release in neuropharmacolgy, effect of (-)-BPAP, a selective enhancer of the impulse propagation mediated release of catecholamines and serotonin in neuropsychopharmacology, etc.. ...
International scientific meeting on the Web, with Keynote Addresses, Invited Symposia, Poster Sessions, and an Exhibitors Foyer. Sessions in basic and clinical sciences, education, and public health. Hosted by McMaster University, Hamilton, Ontario, Canada, Dec 7-16th, 1998. poster Presentation
Lung cancer is the most common cause of cancer death worldwide, with over one million cases annually1. To identify genetic factors that modify disease risk, we conducted a genome-wide association study by analysing 317,139 single-nucleotide polymorphisms in 1,989 lung cancer cases and 2,625 controls from six central European countries. We identified a locus in chromosome region 15q25 that was strongly associated with lung cancer (P = 9 times 10-10). This locus was replicated in five separate lung cancer studies comprising an additional 2,513 lung cancer cases and 4,752 controls (P = 5 times 10-20 overall), and it was found to account for 14% (attributable risk) of lung cancer cases. Statistically similar risks were observed irrespective of smoking status or propensity to smoke tobacco. The association region contains several genes, including three that encode nicotinic acetylcholine receptor subunits (CHRNA5, CHRNA3 and CHRNB4). Such subunits are expressed in neurons and other tissues, in ...
GABAergic interneurons have been shown to be a major target of cholinergic inputs to the hippocampus. Because these interneurons project to pyramidal neurons as well as other interneurons, activation of the cholinergic system is likely to produce a complex modulation of local inhibitory activity. To better understand the role of postsynaptic alpha7 nicotinic acetylcholine receptors in the hippocampus, we have characterized the effects of nicotinic agents on local interneurons of the rat CAI stratum oriens in terms of activation, desensitization, and region of axonal termination. Fast application of acetylcholine onto stratum oriens interneurons during whole-cell recordings from hippocampal slices activated the majority of cells tested, and these responses were mediated almost entirely by alpha7 nicotinic acetylcholine receptors. Anatomical reconstructions showed no clear relationship between the acetylcholine responsivity of interneurons and the regions to which their axons project. Currents mediated by
The nicotinic acetylcholine receptor (nAChR) was first characterized in 1970 as a membrane receptor of a neurotransmitter and an ion channel. nAChRs have been shown to be involved in smoking-induced cancer formation in multiple types of human cancer cells. In vitro and in vivo animal studies have shown that homopentameric nAChR inhibitors, such as methyllycaconitine and α-Bgtx, can attenuate nicotine-induced proliferative, angiogenic, and metastatic effects in lung, colon, and bladder cancer cells. Recent publications have shown that α9-nAChR is important for breast cancer formation, and in many in vivo studies, α9-nAChR-specific antagonists (e.g/, α-ImI, α-ImI, Vc1.1, RgIA, and It14a) produced an analgesic effect. Vc1.1 functions in a variety of animal pain models and currently has entered phase II clinical trials. For cancer therapy, natural compounds such as garcinol and EGCG have been found to block nicotine- and estrogen-induced breast cancer cell proliferation through inhibition of ...
The muscle acetylcholine receptor consiststs of 5 subunits of 4 different types: 2 alpha subunits and 1 each of the beta, gamma, and delta subunits. This gene encodes an alpha subunit that plays a role in acetlycholine binding/channel gating. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Nov 2012 ...
Our laboratory has previously reported that bronchial epithelial cells (BEC) express a regulatory cascade of classic neurotransmitters and receptors that communicate in an almost neuronal-like manner to achieve physiologic regulation. In this paper we show that the similarity between neurotransmitter signaling in neurons and BEC extends to the level of transmitter receptor allosteric modulators. Lynx1 is a member of the ly-6/three finger superfamily of proteins, many of which modulate receptor signaling activity. Lynx1 specifically has been shown to modulate nicotinic acetylcholine receptor (nAChR) function in neurons by altering receptor sensitivity and desensitization. We now report that lynx1 forms a complex with α7 nAChR in BEC and serves to negatively regulate α7 downstream signaling events. Treatment of primary cultures of BEC with nicotine increased levels of nAChR subunits and that increase was potentiated by lynx1 knockdown. Lynx1 knockdown also potentiated the nicotine-induced ...
Studies using mice with β4 nicotinic acetylcholine receptor (nAChR) subunit deficiency (β4-/mice) helped reveal the roles of this subunit in bradycardiac response to vagal stimulation, nicotine-induced seizure activity and anxiety. In order to identify genes that might be related to β4-containing nAChRs activity, we compared the mRNA expression profiles of brains from β4-/and wild-type mice using Affymetrix U74Av2 microarray. Seventy-seven genes significantly differentiated between these two experimental groups. Of them, the two most downregulated were Spg21 and Pts genes. Since the targeted mutagenesis of the β4 nAChR subunit was done by using two mouse strains, 129SvEv and C57BL/6J, it is possible that the genes closely linked to the mutated β4 gene represent the 129SvEv allele and not the control C57BL/6J-driven allele. We examined this possibility by using public database and quantitative RT-PCR. The expression levels of Spg21 and Pts genes that, like the β4 gene, are localized on mouse
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
α3 was the first mammalian neuronal nAChR subunit cloned (Boulter et al., 1986) and one of the first to be studied in an heterologous expression system (Boulter et al., 1987). The immunochemical study by Flores et al. (1996) established the existence of α3β4 nAChRs in the rat trigeminal ganglion, but functional (Zoli et al., 1998; Quick et al., 1999; Grady et al., 2001), immunohistochemical (Yeh et al., 2001), and binding (Whiteaker et al., 2000a) studies have provided only circumstantial evidence for central expression of α3* nAChRs. The findings of the present study provide the first direct evidence for α3* nAChR expression in the mammalian CNS.. Expression of [125I]α-CtxMII-binding sites is independent of α3 nAChR subunit expression in 16 of the 18 regions in which these sites were identified (Fig. 2). These data indicate that [125I]α-CtxMII-binding nAChRs are largely not α3-dependent, despite being found in regions (the optic tract and its associated nuclei and dopaminergic terminal ...
The goal of Dr. Picciottos research team is to understand the role of single molecules in complex behaviors related to addiction, depression, feeding and learning. She and her colleagues use molecular genetic and pharmacological approaches to link the biochemical, cellular, and anatomical levels of investigation to behavior. Of primary interest is the role of acetylcholine and nicotinic acetylcholine receptors in brain function and development.. Dr. Picciottos laboratory also studies signaling molecules downstream of nicotinic receptors, such as calcineurin, CaM kinases and adducins, which may mediate long-term changes in behavior downstream of these receptors.. Specialized Terms: Neuroscience; Molecular basis of behavior; Intracellular signaling; Mouse genetic ...
Mullen, G.; Napier, A.; Balestra, M.; Decory, T.; Hale, G.; Macor, J.; Mack, R.; Loch J, J.; Wu, E. (2000). "(-)-Spiro1-azabicyclo2.2.2octane-3,5-oxazolidin-2-one, a conformationally restricted analogue of acetylcholine, is a highly selective full agonist at the alpha 7 nicotinic acetylcholine receptor". Journal of Medicinal Chemistry 43 (22): 4045-4050. PMID 11063601. doi:10.1021/jm000249r. ...
Grimster, N.P., Stump, B., Fotsing, J.R., Weide, T., Talley, T.T., Yamauchi, J.G., Nemecz, A., Kim, C., Ho, K.-Y., Sharpless, K.B., Taylor, P., Fokin, V.V. Generation of Candidate Ligands for Nicotinic Acetylcholine Receptors Via in Situ Click Chemistry with a Soluble Acetylcholine Binding Protein Template. J. Am. Chem. Soc. 2012, 134, 6732-6740 ...
London, April 8 (ANI): University of Illinois researchers say have mapped the interior of a key component of the relay system that allows the neurotransmitter acetylcholine to carry impulses from neurons to skeletal muscle
DI-fusion, le Dépôt institutionnel numérique de lULB, est loutil de référencementde la production scientifique de lULB.Linterface de recherche DI-fusion permet de consulter les publications des chercheurs de lULB et les thèses qui y ont été défendues.
Kupferausgetauschte Zeolithe vom Typ ZSM-5 wurden mit Hilfe von Adsorptionsmessungen und 129Xe-NMR-spektroskopischen Untersuchungen nach verschiedenen Präparationsverfahren (Austausch aus flüssiger Phase und Festkörperionenaustausch) und verschiedenen Präparations-schritten (Dehydratisieren, Reduktion, Oxidation) untersucht. Zur quantitativen Analyse der erhaltenen Meßwerte wurde ein Modell aufgestellt, mit dessen Hilfe insbesondere die Konzentrationen verschiedener Kupfer-Zentren in den Kanälen ermittelt werden konnten. Nach Reduktion mit CO befanden sich Cu+-Zentren in den Kanälen; nach Oxidation mit O2 waren Cu2+-Kationen entstanden, die sich nicht in den Kanälen befanden und somit für Adsorptive nicht direkt zugänglich waren. Nach Komplexierung mit Ammoniak befanden sich Cu2+-Kationen in den Kanälen, von denen auch nach der Desorption des Ammoniaks zumindest ein Teil innerhalb der Kanäle verblieb. Nach Reduktion mit H2 war die Konzentration der kationischen Zentren innerhalb der ...
TY - JOUR. T1 - Interaction of benzylidene-anabaseine analogues with agonist and allosteric sites on muscle nicotinic acetylcholine receptors. AU - Arias, H. R.. AU - Xing, H.. AU - MacDougall, K.. AU - Blanton, M. P.. AU - Soti, F.. AU - Kern, W. R.. PY - 2009/5/1. Y1 - 2009/5/1. N2 - Background and purpose: Benzylidene-anabaseines (BAs) are partial agonists of the α7 nicotinic acetylcholine receptor (nAChR) but their mechanism(s) of action are unknown. Our study explores several possibilities, including direct interactions of BAs with the nAChR channel. Experimental approach: Functional and radioligand-binding assays were used to examine the interaction of two BA analogues, 3-(2,4-dimethoxybenzylidene)-anabaseine (DMXBA) and Its primary metabolite 3-(4-hydroxy-2-methoxybenzylidene)anabaseine (4OH-DMXBA) with both agonist and non-competitive antagonist (NCA)-bindlng sites on muscle-type nAChRs. Key results: Both BAs non-competitively inhibited ACh activation of human fetal muscle nAChRs and ...
The extremely potent and selective nicotinic acetylcholine receptor antagonist methyllycaconitine, MLA, and related norditerpene alkaloids are finding increasing use as neurochemical probes and as targets for structure-activity relationship studies. In this work, an assay procedure for MLA which utilises ion suppression reverse-phase HPLC with UV absorbance detection at 270 nm is described. The method detected 280 ng MLA on column.
This gene encodes a nicotinic acetylcholine receptor, which belongs to a superfamily of ligand-gated ion channels that play a role in fast signal transmission at synapses. These pentameric receptors can bind acetylcholine, which causes an extensive change in conformation that leads to the opening of an ion-conducting channel across the plasma membrane. This protein is an integral membrane receptor subunit that can interact with either nAChR beta-2 or nAChR beta-4 to form a functional receptor. Mutations in this gene cause nocturnal frontal lobe epilepsy type 1. Polymorphisms in this gene that provide protection against nicotine addiction have been described. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012 ...
Five cases of severe neutropenia (neutrophil counts < 0.5 per 109 cells/L) associated with exposure to cocaine and levamisole, an antihelimithic agent no longer available in Canada, were identified in Alberta in 2008. Alberta and British Columbia (BC) public health officials issued an advisory and urged health care professionals to report cases to public health. This paper presents the findings of the public health investigations. Cases were identified prospectively through reporting by clinicians and a retrospective review of laboratory and medical examiners data from January 1, 2006 to March 31, 2009. Cases were categorized as confirmed, probable or suspect. Only the confirmed and probable cases are included in this paper. We compare cases of severe neutropenia associated with tainted cocaine (NATC) identified in Alberta and BC between January 1, 2008 to March 31, 2009. Of the 42 NATC cases: 23(55%) were from Alberta; 19(45%) were from British Columbia; 57% of these cases reported crack cocaine use
Binding of 125 I a-bungarotoxin to acetylcholine receptors of a ganglionic homogenate of the marine mollusc Aplysia is blocked by the anticholinesterases eserine and neostigmine. Eserine and neostigmine also block toxin binding to a solubilized receptor preparation. Unlike their relative potency in blocking toxin binding, neostigmine is a more potent inhibitor of Aplysia acetylcholinesterase than is eserine. alpha-Bungarotoxin does not affect esterase activity or interfere with the ability of eserine to block the esterase. The response to acetylcholine recorded through intracellular microelectrodes is blocked by alpha-bungarotoxin. Neither eserine nor neostigmine blocks the acetylcholine response, but rather prolongs and increases it as expected from their effects on the esterase. Eserine blocks the alpha-bungarotoxin inhibition of the physiologic acetylcholine response. These results indicate that eserine and neostigmine block the binding of alpha-bungarotoxin by interacting with a site which is
The nicotinic acetylcholine receptor (AcChoR) of Torpedo electroplax is a multisubunit transmembrane glycoprotein complex with a subunit stoichiometry of alpha 2 beta gamma delta. The RNAs for the separate subunits were transcribed in vitro from cDNAs inserted in pSP64T vectors and microinjected in Xenopus oocytes. Microinjected in vitro-transcribed RNAs were stable, with a half-life of 72 hr. Xenopus oocytes assembled functional AcChoRs from the subunit-specific RNAs. These receptors were inserted in the cell membrane and could be detected as early as 6 hr after RNA microinjection. The oocyte-expressed AcChoR subunits could be immunoprecipitated with anti-Torpedo AcChoR subunit antibodies. Expression of the AcChoR in oocytes proceeded linearly for 72 hr after microinjection. While the amount of RNA injected did not alter the linearity of the expression time course, the rate of receptor expression in oocytes showed a saturable dependence on RNA concentration. Varying the relative amount of ...

Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation.  - PubMed - NCBINicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. - PubMed - NCBI

Here we report that the nicotinic acetylcholine receptor alpha7 subunit is required for acetylcholine inhibition of macrophage ... but fails to inhibit TNF synthesis in alpha7-deficient mice. Thus, the nicotinic acetylcholine receptor alpha7 subunit is ... Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation.. Wang H1, Yu M, Ochani M, Amella CA ... the identity of the essential macrophage acetylcholine-mediated (cholinergic) receptor that responds to vagus nerve signals was ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/12508119?dopt=Abstract

Rabbit retinal ganglion cells express functional alpha7 nicotinic acetylcholine receptors.  - PubMed - NCBIRabbit retinal ganglion cells express functional alpha7 nicotinic acetylcholine receptors. - PubMed - NCBI

Rabbit retinal ganglion cells express functional alpha7 nicotinic acetylcholine receptors.. Strang CE1, Andison ME, Amthor FR, ... We sought to determine whether functional alpha(7) nicotinic acetylcholine receptors (nAChRs) contribute to the responses of ... but the specific receptor subtypes involved in mediating these effects have been only partially characterized. ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/15872006

Structural determinants for interaction of partial agonists with acetylcholine binding protein and neuronal alpha7 nicotinic...Structural determinants for interaction of partial agonists with acetylcholine binding protein and neuronal alpha7 nicotinic...

... for interaction of partial agonists with acetylcholine binding protein and neuronal alpha7 nicotinic acetylcholine receptor.. ... is a soluble surrogate of the ligand binding domain of nicotinic acetylcholine receptors. Agonists bind within a nest of ... two partial agonists selectively activating the alpha7 receptor, 3-(2,4-dimethoxybenzylidene)-anabaseine and its 4-hydroxy ... This study, while pointing to loop F as a major determinant of receptor subtype selectivity, also identifies a new template ...
more infohttps://www.uniprot.org/citations/19696737

MODULATION OF THE ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTOR FOLLOWING E by Thomas Matt Woodcock"MODULATION OF THE ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTOR FOLLOWING E" by Thomas Matt Woodcock

MODULATION OF THE ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTOR FOLLOWING EXPERIMENTAL RAT BRAIN INJURY IMPROVES CELLULAR AND ... Woodcock, Thomas Matt, "MODULATION OF THE ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTOR FOLLOWING EXPERIMENTAL RAT BRAIN INJURY ...
more infohttps://uknowledge.uky.edu/gradschool_diss/770/

Nicotine exposure reduces N-methyl-D-aspartate toxicity in the hippocampus: relation to distribution of the alpha7 nicotinic...Nicotine exposure reduces N-methyl-D-aspartate toxicity in the hippocampus: relation to distribution of the alpha7 nicotinic...

Examination of distinct receptor subtypes in promoting neuronal survival is of importance not only in understanding the ... MATERIAL AND METHODS The present studies examined the relationship between distribution of alpha7 subunit-bearing nAChRs, using ... CONCLUSIONS The neuroprotective effect of nicotine against excitotoxicity, then, is not directly related to alpha7 subunit ... Localization of the alpha7 subunit was varied with no binding observed in the dentate gyrus, low density in the CA3 and CA1 ...
more infohttps://www.semanticscholar.org/paper/Nicotine-exposure-reduces-N-methyl-D-aspartate-in-Prendergast-Harris/436b584fefda6774681a21894b253876f85659ae

Towards an understanding of human alpha-7 nicotinic acetylcholine receptor selectivity : the creation and characterization of a...Towards an understanding of human alpha-7 nicotinic acetylcholine receptor selectivity : the creation and characterization of a...

... of acetylcholine from presynaptic neurons triggers activation through channel opening of the nicotinic acetylcholine receptors ... but the protein generated served to identify structurally a glycosylation site on the receptor as well as proved to be a better ... and stimulation of the neurotransmitter acetylcholine. At the synaptic cleft, the release ... distinguishing characteristics that may contribute to ligand selectivity and structural components that contribute to receptor ...
more infohttps://escholarship.org/uc/item/46t749dj

Effects of the alpha7 nicotinic acetylcholine receptor agonist GTS-21 on the innate immune response in humansEffects of the alpha7 nicotinic acetylcholine receptor agonist GTS-21 on the innate immune response in humans

... ... to the alpha7 nicotinic ACh receptor (alpha7nAChR). We recently reported potent anti-inflammatory effects of the alpha7nAChR ... The vagus nerve can reflexively attenuate the innate immune response via binding of the vagal neurotransmitter acetylcholine ( ...
more infohttps://repository.ubn.ru.nl/handle/2066/96863

Inhibitory role of cholinergic system mediated via alpha7 nicotinic acetylcholine receptor in LPS-in | Page 2 | Phoenix Rising...Inhibitory role of cholinergic system mediated via alpha7 nicotinic acetylcholine receptor in LPS-in | Page 2 | Phoenix Rising...

Inhibitory role of cholinergic system mediated via alpha7 nicotinic acetylcholine receptor in LPS-in. Discussion in Other ... Abstract: We studied the involvement of nicotinic acetylcholine receptors (nAChRs) in the. inflammation-related activity of ... Functional role of the nicotinic arm of the acetylcholine regulatory axis in human B-cell lines. Juan Arredondo1 Denys ... suggested that signaling through the nicotinic arm of acetylcholine regulatory axis is important. for B-cell involvement in ...
more infohttp://forums.phoenixrising.me/index.php?threads/inhibitory-role-of-cholinergic-system-mediated-via-alpha7-nicotinic-acetylcholine-receptor-in-lps-in.21086/page-2

EP 1315494 A1 20030604 - AGENT FOR MODULATING EXCITATORY SYNAPTIC TRANSMISSION COMPRISING A COMPOUND HAVING ALPHA-7 NICOTINIC...EP 1315494 A1 20030604 - AGENT FOR MODULATING EXCITATORY SYNAPTIC TRANSMISSION COMPRISING A COMPOUND HAVING ALPHA-7 NICOTINIC...

... agent for modulating excitatory synaptic transmission which contains a compound having alpha 7 nicotinic acetylcholine receptor ... agent for modulating excitatory synaptic transmission which contains a compound having alpha 7 nicotinic acetylcholine receptor ... an agent for modulating excitatory synaptic transmission which comprises using alpha 7 nicotinic acetylcholine receptor ... an agent for modulating excitatory synaptic transmission which comprises using alpha 7 nicotinic acetylcholine receptor ...
more infohttps://data.epo.org/gpi/EP1315494A1-AGENT-FOR-MODULATING-EXCITATORY-SYNAPTIC-TRANSMISSION-COMPRISING-A-COMPOUND-HAVING-ALPHA-7-NICOTINIC-ACETYLCHOLINE-RECEPTOR-ACTIVATION-PROPERTY

Fachrepositorium Lebenswissenschaften: Distribution of the nicotinic acetylcholine receptor subunits alpha4 and alpha7 in the...Fachrepositorium Lebenswissenschaften: Distribution of the nicotinic acetylcholine receptor subunits alpha4 and alpha7 in the...

Distribution of the nicotinic acetylcholine receptor subunits alpha4 and alpha7 in the human foetal brain * Lain, Felicitas U. ... Distribution of the nicotinic acetylcholine receptor subunits alpha4 and alpha7 in the human foetal brain , ... Distribution of the nicotinic acetylcholine receptor subunits alpha4 and alpha7 in the human foetal brain , ... Distribution of the nicotinic acetylcholine receptor subunits alpha4 and alpha7 in the human foetal brain. *StreamGate.pdf. ...
more infohttps://repository.publisso.de/resource/frl:2846831

Anti-Nicotinic Acetylcholine Receptor alpha 7 antibody (ab10096) ReferencesAnti-Nicotinic Acetylcholine Receptor alpha 7 antibody (ab10096) References

Anti-Nicotinic Acetylcholine Receptor alpha 7 antibody (ab10096) has been cited in 24 publications. References for Human, Mouse ... Plummer HK et al. Expression of the alpha7 nicotinic acetylcholine receptor in human lung cells. Respir Res 6:29 (2005). PubMed ... Paulo JA et al. Proteomic analysis of an alpha7 nicotinic acetylcholine receptor interactome. J Proteome Res 8:1849-58 (2009). ... Machaalani R et al. Distribution of nicotinic acetylcholine receptor subunits alpha7 and beta2 in the human brainstem and ...
more infohttp://www.abcam.com/nicotinic-acetylcholine-receptor-alpha-7-antibody-ab10096-references.html

Human Nicotinic Acetylcholine Receptor alpha 7 peptide (ab24285)Human Nicotinic Acetylcholine Receptor alpha 7 peptide (ab24285)

Buy our Human Nicotinic Acetylcholine Receptor alpha 7 peptide. Ab24285 is a blocking peptide for ab23832 and has been ... Cellular distribution of the nicotinic acetylcholine receptor alpha7 subunit in rat hippocampus.. Neurosci Res 65:296-306 (2009 ... Human Nicotinic Acetylcholine Receptor alpha 7 peptide. See all Nicotinic Acetylcholine Receptor alpha 7 proteins and peptides ... Suitability of Nicotinic Acetylcholine Receptor a7 and Muscarinic Acetylcholine Receptor 3 Antibodies for Immune Detection: ...
more infohttp://www.abcam.com/human-nicotinic-acetylcholine-receptor-alpha-7-peptide-ab24285.html

Research Keyword Faculty Listing | Yale School of MedicineResearch Keyword Faculty Listing | Yale School of Medicine

alpha7 Nicotinic Acetylcholine Receptor. Kelly Cosgrove, PhD Associate Professor of Psychiatry, of Radiology and Biomedical ... Alcoholism; alpha7 Nicotinic Acetylcholine Receptor; Brain; Chemicals and Drugs; Diseases; Neurobiology; Neuroimaging; Nicotine ... alpha7 Nicotinic Acetylcholine Receptor; Apoptosis; ATP Synthetase Complexes; Mitochondria; Neurodegenerative Diseases View ...
more infohttps://medicine.yale.edu/research/listing.aspx?meshId=27037

Mitochondrial Reactive Oxygen Species Inactivate Neuronal Nicotinic Acetylcholine Receptors and Induce Long-Term Depression of...Mitochondrial Reactive Oxygen Species Inactivate Neuronal Nicotinic Acetylcholine Receptors and Induce Long-Term Depression of...

1999) The alpha7 nicotinic acetylcholine receptor in neuronal plasticity. Mol Neurobiol 20:1-16. ... 2007) Nicotinic acetylcholine receptors and nicotinic cholinergic mechanisms of the central nervous system. Annu Rev Pharmacol ... 2006) Brain nicotinic acetylcholine receptors: native subtypes and their relevance. Trends Pharmacol Sci 27:482-491. ... Neuronal nicotinic acetylcholine receptors (nAChRs), ligand-gated ion channels implicated in a variety of cognitive, motor, and ...
more infohttp://www.jneurosci.org/content/28/7/1733

Nicotinic Acetylcholine Receptor-Based Blockade: Applications of Molecular Targets for Cancer Therapy | Clinical Cancer ResearchNicotinic Acetylcholine Receptor-Based Blockade: Applications of Molecular Targets for Cancer Therapy | Clinical Cancer Research

... and ImII target distinct regions of the human alpha7 nicotinic acetylcholine receptor and distinguish human nicotinic receptor ... Nicotinic acetylcholine receptors of muscle and neuronal (alpha7) types coexpressed in a small cell lung carcinoma. J Neurochem ... The alpha7 nicotinic acetylcholine receptor in neuronal plasticity. Mol Neurobiol 1999;20:1-16. ... Microglial alpha7 nicotinic acetylcholine receptors drive a phospholipase C/IP3 pathway and modulate the cell activation toward ...
more infohttp://clincancerres.aacrjournals.org/content/17/11/3533

JCI -
Nicotine exposure and bronchial epithelial cell nicotinic acetylcholine receptor expression in the pathogenesis of lung...JCI - Nicotine exposure and bronchial epithelial cell nicotinic acetylcholine receptor expression in the pathogenesis of lung...

Human bronchial epithelial and endothelial cells express alpha7 nicotinic acetylcholine receptors. Mol. Pharmacol. 2001. 60: ... Janus kinase 2: an early target of Alpha7-mediated nicotinic acetylcholine receptor neuroprotection against Abeta (1-42) ... Nonstandard abbreviations used: nicotinic acetylcholine receptor (nAchR); acetylcholine (Ach); N′Nitrosonornicotine (NNN); 4( ... Nicotine activates the extracellular signal-regulated kinase 1/2 via the alpha7 nicotinic acetylcholine receptor and protein ...
more infohttps://www.jci.org/articles/view/17492

α7 Nicotinic Acetylcholine Receptor (α7nAChR) Expression in Bone Marrow-Derived Non-T Cells Is Required for the Inflammatory...α7 Nicotinic Acetylcholine Receptor (α7nAChR) Expression in Bone Marrow-Derived Non-T Cells Is Required for the Inflammatory...

1999) The alpha7 nicotinic acetylcholine receptor in neuronal plasticity. Mol. Neurohiol. 20:1-16.CrossRefGoogle Scholar ... 2003) Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature. 421:384-8.CrossRef ... 2007) Selective alpha7-nicotinic acetylcholine receptor agonist GTS-21 improves survival in murine endotoxemia and severe ... 2006) Coex-pression and spatial association of nicotinic acetyl-choline receptor subunits alpha7 and alpha10 in rat sympathetic ...
more infohttps://rd.springer.com/article/10.2119%2Fmolmed.2011.00405

α7-Containing and Non-α7-Containing Nicotinic Receptors Respond Differently to Spillover of Acetylcholine | Journal of...α7-Containing and Non-α7-Containing Nicotinic Receptors Respond Differently to Spillover of Acetylcholine | Journal of...

2001) Ultrastructural distribution of the alpha7 nicotinic acetylcholine receptor subunit in rat hippocampus. J Neurosci 21: ... 2007) Nicotinic acetylcholine receptors and nicotinic cholinergic mechanisms of the central nervous system. Annu Rev Pharmacol ... 1997) Choline is a selective agonist of α7 nicotinic acetylcholine receptors in the rat brain neurons. Eur J Neurosci 9:2734- ... 2007) Ca2+ flux and signaling implications by nicotinic acetylcholine receptors in rat medial habenula. J Neurophysiol 97:83-92 ...
more infohttp://www.jneurosci.org/content/31/42/14920

Prestwick Chemical presents some case studies from past success storiesPrestwick Chemical presents some case studies from past success stories

Alpha-7 Nicotinic acetylcholine receptor modulators. Prestwicks team developed for this customer the medicinal chemistry ... we developed positive allosteric modulators of the metabotropic glutamate type-4 receptor (mGluR4 PAMs). Starting from one ... program in the hot field of Alpha-7 nAChR allosteric modulation for cognitive function recovery in neurodegenerative diseases. ...
more infohttp://prestwickchemical.com/services-success-stories-casestudy.html

Frontiers | The Sleep-Wake Cycle in the Nicotinic Alpha-9 Acetylcholine Receptor Subunit Knock-Out Mice | Frontiers in Cellular...Frontiers | The Sleep-Wake Cycle in the Nicotinic Alpha-9 Acetylcholine Receptor Subunit Knock-Out Mice | Frontiers in Cellular...

Nicotinic alpha-9 acetylcholine receptor subunit (alpha-9 nAChR) participate in physiological processes occurring in sensory, ... Nicotinic alpha-9 acetylcholine receptor subunit (alpha-9 nAChR) participate in physiological processes occurring in sensory, ... Acetylcholine receptors in the retinas of the alpha7 nicotinic acetylcholine receptor knockout mouse. Mol. Vis. 20, 1328-1356. ... The Sleep-Wake Cycle in the Nicotinic Alpha-9 Acetylcholine Receptor Subunit Knock-Out Mice. Natalia Madrid-López1,2, Jorge ...
more infohttps://www.frontiersin.org/articles/10.3389/fncel.2017.00302/full

Nicotinic acetylcholine receptor expression by directionally selective ganglion cells | Visual Neuroscience | Cambridge CoreNicotinic acetylcholine receptor expression by directionally selective ganglion cells | Visual Neuroscience | Cambridge Core

Nicotinic acetylcholine receptor expression by directionally selective ganglion cells - Volume 24 Issue 4 - CHRISTIANNE E. ... Choline is a selective agonist of alpha7 nicotinic acetylcholine receptors in the rat brain neurons. European Journal of ... Lindstrom, J.M. (1996). Neuronal nicotinic acetylcholine receptors. In Ion Channels, Vol. 4, ed. Narahashi, T., pp. 377-449. ... Nicotinic acetylcholine receptor expression by directionally selective ganglion cells. * CHRISTIANNE E. STRANG (a1), JORDAN M. ...
more infohttps://www.cambridge.org/core/journals/visual-neuroscience/article/nicotinic-acetylcholine-receptor-expression-by-directionally-selective-ganglion-cells/32C9A0906E66E744C3ABA2A4D9C80B28

Prenatal restraint stress decreases the expression of alpha-7 nicotinic receptor in the brain of adult rat offspring. -...Prenatal restraint stress decreases the expression of alpha-7 nicotinic receptor in the brain of adult rat offspring. -...

... hypothalamic-pituitary-adrenal axis dysfunction and loss of cholinergic neurons and neuronal nicotinic acetylcholine receptors ... Focus on Vagus Nerve Stimulation and Activation of the Alpha-7 Nicotinic Acetylcholine Receptor. *Fabiana Maria das Graças ... Brain nicotinic acetylcholine receptors: native subtypes and their relevance.. *Cecilia Gotti, Michele Zoli, Francesco Clementi ... Early Life Stress, Nicotinic Acetylcholine Receptors and Alcohol Use Disorders. *Joan Y Holgate, Selena E Bartlett, Marcelo ...
more infohttps://www.semanticscholar.org/paper/Prenatal-restraint-stress-decreases-the-expression-Baier-Pallar%C3%A9s/8186017d7ec1b79efd5b20437bc07acaf75a1bab
  • In a collaborative approach with Domain Therapeutics (Strasbourg-Illkirch, France) providing their cutting edge FRET assay technology DETECT-ALL for identifying GPCR ligands, we developed positive allosteric modulators of the metabotropic glutamate type-4 receptor (mGluR4 PAMs). (prestwickchemical.com)
  • The work presented here uses a comprehensive approach including structural studies, protein engineering, functional studies, and protein characterization to gain insight into the distinguishing characteristics that may contribute to ligand selectivity and structural components that contribute to receptor function. (escholarship.org)
  • Humoral mechanisms that restrain or inhibit these damaging responses include glucocorticoid hormones, soluble cytokine receptors, IL-10, transforming growth factor (TGF)-β and other antiinflammatory cytokines. (springer.com)
  • Furthermore, deleting α7nAChR from isolated macrophages impairs the ability of acetylcholine to suppress TNF and other cytokines. (springer.com)
  • Our results provide insight for the further development of nicotinic therapeutics and will be useful to direct future experiments with protein structure-based modeling and site-directed mutagenesis. (aspetjournals.org)
  • Electrical stimulation of the vagus nerve inhibits TNF synthesis in wild-type mice, but fails to inhibit TNF synthesis in alpha7-deficient mice. (nih.gov)
  • Acetylcholine acts on androgen receptor to promote the migration and invasion but inhibit the apoptosis of human hepatocarcinoma. (abcam.com)
  • This hyporesponsiveness can be reversed in vitro by stimulation via the T-cell receptor (TCR) and high concentrations of IL-2. (aspetjournals.org)
  • however, the intracellular regulatory pathways that produce these receptor-modifying actions are not fully understood. (jneurosci.org)
  • Compounds in filled gray circles had no significant agonist activity when tested at 300 μMon α7, α4β2, or α3β4 receptors (data not shown). (aspetjournals.org)