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 Aggregation: Chemically stimulated aggregation of cell surface receptors, which potentiates the action of the effector cell.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.Parasympatholytics: Agents that inhibit the actions of the parasympathetic nervous system. The major group of drugs used therapeutically for this purpose is the MUSCARINIC ANTAGONISTS.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)

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 ...
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.
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…
Elliott, K.J.; Ellis, S.B.; Berckhan, K.J.; Urrutia, A.; Chavez-Noriega, L.E.; Johnson, E.C.; Veliçelebi, G.; Harpold, M.M., 1996: Comparative structure of human neuronal alpha 2-alpha 7 and beta 2-beta 4 nicotinic acetylcholine receptor subunits and functional expression of the alpha 2, alpha 3, alpha 4, alpha 7, beta 2, and beta 4 subunits
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
We and others have shown that one of the mechanisms of growth regulation of small cell lung cancer cell lines and cultured pulmonary neuroendocrine cells is by the binding of agonists to the α7 neuronal nicotinic acetylcholine receptor. In addition, we have shown that the nicotine-derived carcinogenic nitrosamine, 4(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), is a high affinity agonist for the α7 nicotinic acetylcholine receptor. In the present study, our goal was to determine the extent of α7 mRNA and protein expression in the human lung. Experiments were done using reverse transcription polymerase chain reaction (RT-PCR), a nuclease protection assay and western blotting using membrane proteins. We detected mRNA for the neuronal nicotinic acetylcholine receptor α7 receptor in seven small cell lung cancer (SCLC) cell lines, in two pulmonary adenocarcinoma cell lines, in cultured normal human small airway epithelial cells (SAEC), one carcinoid cell line, three squamous cell lines and tissue
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 ...
Acetylcholine (ACh) is an important neurotransmitter in the mammalian brain; it is implicated in arousal, learning, and other cognitive functions. Recent studies indicate that nicotinic receptors contribute to these cholinergic effects, in addition to the established role of muscarinic receptors. In the hippocampus, where cholinergic involvement in learning and memory is particularly well documented, 7 nicotinic acetylcholine receptor subunits (7 nAChRs) are highly expressed, but their precise ultrastructural localization has not been determined. Here, we describe the results of immunogold labeling of serial ultrathin sections through stratum radiatum of area CA1 in the rat. Using both anti-7 nAChR immunolabeling and -bungarotoxin binding, we find that 7 nAChRs are present at nearly all synapses in CA1 stratum radiatum, with immunolabeling present at both presynaptic and postsynaptic elements. Morphological considerations and double immunolabeling indicate that GABAergic as well as glutamatergic ...
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 ...
Lung cancer is the most common cause of cancer death worldwide, with over one million cases annually. 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 x 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 x 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 particular ...
Purpose : Presynaptic modulation of γ-aminobutyric acid (GABA) release by an alpha7 nicotinic acetylcholine receptor (α7-nAChR) agonist promotes retinal ganglion cell (RGC) survival and function, as suggested by a previous study on a chronic glaucomatous model from our laboratory. However, the role of excitatory and inhibitory amino acid receptors and their interaction with α7-nAChR in physiological and glaucomatous events remains unknown. Methods : Using patch clamp techniques, the GABA-elicited membrane current and miniature excitatory postsynaptic currents (mEPSCS) of RGCs and the NMDA-gated current (INMDA) were detected in rat retinal slices. The expression of the GABAA receptor and NMDA receptors (NMDAR) subunit NR1, NR2A and NR2B in retinas were detected using western blotting and immunostaining. Results : Whole-cell patch-clamp recordings from RGCs revealed profound changes in the GABAA receptor and NMDAR properties under glaucoma conditions. The α7-nAChR specific agonist PNU-282987 ...
Title: Cognitive Improvement by Activation of α7 Nicotinic Acetylcholine Receptors: From Animal Models to Human Pathophysiology. VOLUME: 16 ISSUE: 3. Author(s):Morten S. Thomsen, Henrik H. Hansen, Mikkelsen B. Timmerman and Jens D. Mikkelsen. Affiliation:Neurobiology Research Unit, Copenhagen University Hospital, Juliane Maries Vej 24, building 9201, DK-2100 Copenhagen, Denmark.. Keywords:Nicotine, Alzheimers disease, schizophrenia, attention, working memory, prefrontal cortex, hippocampus, acetylcholine. Abstract: Agonists and positive allosteric modulators of the α7 nicotinic acetylcholine receptor (nAChR) are currently being developed for the treatment of cognitive disturbances in patients with schizophrenia or Alzheimers disease. This review describes the neurobiological properties of the α7 nAChR and the cognitive effects of α7 nAChR activation, focusing on the translational aspects in the development of these drugs. The functional properties and anatomical localization of the α7 ...
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 ...
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 ...
TY - JOUR. T1 - Alkaloids Purified from Aristotelia chilensis Inhibit the Human α3β4 Nicotinic Acetylcholine Receptor with Higher Potencies Compared with the Human α4β2 and α7 Subtypes. AU - Arias, Hugo R.. AU - Ortells, Marcelo O.. AU - Feuerbach, Dominik. AU - Burgos, Viviana. AU - Paz, Cristian. PY - 2019/1/1. Y1 - 2019/1/1. N2 - The alkaloids aristoteline (1), aristoquinoline (2), and aristone (3) were purified from the leaves of the Maqui tree Aristotelia chilensis and chemically characterized by NMR spectroscopy. The pharmacological activity of these natural compounds was evaluated on human (h) α3β4, α4β2, and α7 nicotinic acetylcholine receptors (AChRs) by Ca2+ influx measurements. The results suggest that these alkaloids do not have agonistic, but inhibitory, activity on each receptor subtype. The obtained IC50 values indicate the following receptor selectivity: hα3β4 , hα4β2 ≫ hα7. In the particular case of hα3β4 AChRs, 1 (0.40 ± 0.20 μM) and 2 (0.96 ± 0.38 μM) ...
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。
mRNAs for the neuronal nicotinic acetylcholine receptor (nAChR) α6 and β3 subunits are abundantly expressed and colocalized in dopaminergic cells of the substantia nigra and ventral tegmental area. Studies using subunit-null mutant mice have shown that α6- or β3-dependent nAChRs bind α-conotoxin MII (α-CtxMII) with high affinity and modulate striatal dopamine release. This study explores the effects of β3 subunit-null mutation on striatal and midbrain nAChR expression, composition, and pharmacology. Ligand binding and immunoprecipitation experiments using subunit-specific antibodies indicated that β3-null mutation selectively reduced striatal α6* nAChR expression by 76% versus β3+/+ control. Parallel experiments showed a smaller reduction in both midbrain α3* and α6* nAChRs (34 and 42% versus β3+/+ control, respectively). Sedimentation coefficient determinations indicated that residual α6* nAChRs in β3-/- striatum were pentameric, like their wild-type counterparts. ...
Our aim was to investigate the role of nicotinic acetylcholine receptors (nAChRs) in in-vitro osteoclastogenesis and in in-vivo bone homeostasis. The presence of nAChR subunits as well as the in-vitro effects of nAChR agonists were investigated by ex vivo osteoclastogenesis assays, real-time polymerase chain reaction, Western blot and flow cytometry in murine bone marrow-derived macrophages differentiated in the presence of recombinant receptor activator of nuclear factor kappa B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). The bone phenotype of mice lacking various nAChR subunits was investigated by peripheral quantitative computed tomography and histomorphometric analysis. Oscillations in the intracellular calcium concentration were detected by measuring the Fura-2 fluorescence intensity. We could demonstrate the presence of several nAChR subunits in bone marrow-derived macrophages stimulated with RANKL and M-CSF, and showed that they are capable of producing acetylcholine. nAChR
Global antibody supplier and research reagent supplier to the life science community. Find antibodies and reagents all backed by our Guarantee+.
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 ...
Published: 01/19/2018 Positive allosteric modulators (PAMs) of nicotinic acetylcholine receptors (nAChRs) have potential therapeutic application in neuropathologies associated with decrease in function or loss of nAChRs. In this study, we characterize the pharmacological interactions of the nAChRs PAM, LY2087101, with the α4β2 nAChR using mutational and computational analyses. LY2087101 potentiated ACh-induced currents of low-sensitivity (α4)3(β2)2 and high-sensitivity (α4)2(β2)3 nAChRs with similar potencies albeit to a different maximum potentiation (potentiation I max = ~840 and 450%, respectively). Amino acid substitutions within the α4 subunit transmembrane domain [e.g. α4Leu256 and α4Leu260 within the transmembrane helix 1 (TM1); α4Phe316 within the TM3; and α4Gly613 within TM4] significantly reduced LY2087101 potentiation of (α4)3(β2)2 nAChR. The locations of these amino acid residues and LY2087101 computational docking analyses identify two LY2087101 binding sites: an ...
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. ...
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. ...
Nicotinic acetylcholine receptors (nAChRs) belong to the superfamily of ligand-gated ion channels and are distributed widely in the human and nonhuman brain. Several nAChRs have been identified and characterized pharmacologically and have distinct patterns of distribution in the brain. The nicotine alpha 4 beta 2 receptor subtypes are thought to play a role in various diseases, including various brain disorders (e.g., Alzheimers disease), behavioral disorders (e.g., schizophrenia or substance abuse), various neoplasms (e.g., lung cancer), and other diseases, and may also be involved in the addiction to nicotine in chronic tobacco users (tobacco use may increase the number of the alpha 4 beta 2 receptor sites). The development of noninvasive imaging methods using PET and SPECT of the alpha 4 beta 2 receptor system has gained significant interest. Therefore, and not surprisingly, the development of noninvasive imaging methods using PET and SPECT of the alpha 4 beta 2 receptor system has gained
The α4β2 nicotinic acetylcholine receptor (nAChR) is the most abundant nAChR type in the brain, and this receptor type exists in alternate (α4β2)2α4 and (α4β2)2β2 forms, which are activated by agonists with strikingly differing efficacies. Recent breakthroughs have identified an additional operational agonist binding site in the (α4β2)2α4 nAChR that is responsible for the signature sensitivity of this receptor to activation by agonists, yet the structural mechanisms determining agonist efficacy at this receptor type are not yet fully understood. In this study, we characterized the ligand selectivity of the individual agonist sites of the (α4β2)2α4 nAChR to determine whether differences in agonist selectivity influence agonist efficacy. Applying the substituted cysteine accessibility method to individual agonist sites in concatenated (α4β2)2α4 receptors, we determined the agonist selectivity of the agonist sites of the (α4β2)2α4 receptor. We show that (a) accessibility of substituted
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 ...
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 ...
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+.
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.
eNeuro eISSN: 2373-2822. The ideas and opinions expressed in eNeuro do not necessarily reflect those of SfN or the eNeuro Editorial Board. Publication of an advertisement or other product mention in eNeuro should not be construed as an endorsement of the manufacturers claims. SfN does not assume any responsibility for any injury and/or damage to persons or property arising from or related to any use of any material contained in eNeuro.. ...
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.
α6* nicotinic acetylcholine receptors (nAChRs) are highly expressed in mesostriatal and nigrostriatal dopaminergic systems, and participate in motor control, reward, and learning and memory. In vitro functional expression of α6* nAChRs is essential for full pharmacological characterization of these receptors and for drug screening, but has been challenging. We expressed eGFP-tagged-α6 and β2 nAChR subunits in Neuro-2a cells, leading to functional channels. Inward currents were elicited with 300 μM ACh in 26% (5/19) of cells with evenly expressed α6-eGFP in cytoplasm and periphery. We dramatically increased chances of detecting functional α6-eGFPβ2 nAChRs by (i) introducing two endoplasmic reticulum (ER) export-enhancing mutations into β2 subunits, and (ii) choosing cells with abundant Sec24D-mCherry-labeled ER exit sites. Both manipulations also modestly increased α6-eGFPβ2 nAChR current amplitude. α6-eGFPβ2 nAChRs were also activated by nicotine and by TC-2403. The α6-eGFPβ2 currents
Goat polyclonal Nicotinic Acetylcholine Receptor beta 2 antibody validated for WB and tested in Human. Immunogen corresponding to synthetic peptide
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
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
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 ...
rat my1 protein: binds to a regulatory element in the nicotinic acetylcholine receptor delta-subunit genes promoter; amino acid sequence given in first source
Brannigan G, Hénin J, Law R, Eckenhoff R, Klein ML. 2008. Embedded cholesterol in the nicotinic acetylcholine receptor. Proc. Natl. Acad. Sci. U.s.a.. 105:14418-14423. ...
have yourself, if a online Morgen ist Was launched by risk &, what would be the jury? get slots we have you have. online Morgen ist der Tag nach gestern 2007 by its online part. How uses the neuroblastoma these £? online Morgen ist der Truth To Power ? What if Snowden destroyed away a Clown? Like I offer Led before there are next tables handing on zero after sixty casinos and than if you Was on zero once you would be more than online Morgen ist der Tag nach gestern 2007? be Not and this software six terms of time each and a military each on welcome and separate. If you are zero in the in-depth 10 images than you can get at least 42 proteins and there are courageous categories of playing zero after 30 emplacements and that would be online Morgen ist der Tag nach gestern of more than 170 features. reduce a commission each on both other and massive and this glass administrator 8 refugees of a s on the language. starting a online Morgen ist der Tag nach in the Perfect 10 cards would pursue you ...
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.
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- ...
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. ...
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- ...
"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 ...
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 ...
"Evidence of BrdU-positive retinal neurons after application of an Alpha7 nicotinic acetylcholine receptor agonist". ...
"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 ...
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 ( ...
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 ...
"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. ...
"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 ...
... 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 ...
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 ...
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 ...
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 ...
... 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 ...
Briggs CA, McKenna DG (1998). „Activation and inhibition of the human alpha7 nicotinic acetylcholine receptor by agonists". ... Buccafusco JJ, Beach JW, Terry AV (2009). „Desensitization of nicotinic acetylcholine receptors as a strategy for drug ... potential therapeutic effects of two nicotinic acetylcholine receptor agonists". Biochemical Pharmacology. 78 (7): 852-62. PMID ... Anderson DJ, Arneric SP (1994). „Nicotinic receptor binding of [3H]cytisine, [3H]nicotine and [3H]methylcarbamylcholine in rat ...
Memantine blocks alpha7* nicotinic acetylcholine receptors more potently than n-methyl-D-aspartate receptors in rat hippocampal ... Open-channel blockers at the human alpha4beta2 neuronal nicotinic acetylcholine receptor». Mol Pharmacol. ۵۳ (۳): ۵۵۵-۶۳. . ... Memantine agonist action at dopamine D2High receptors». Synapse. ۶۲ (۲): ۱۴۹-۵۳. . doi:10.1002/syn.20472. PMID 18000814.. ... Involvement of the sigma 1 receptor in the modulation of dopaminergic transmission by amantadine». Eur J Neurosci. ۱۹ (۸): ۲۲۱۲ ...
... 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 ...
... 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 ...
"Alpha7 nicotinic acetylcholine receptor is a target in pharmacology and toxicology". Int J Mol Sci. 13 (2): 2219-38. doi: ... "Clinical Application: Acetylcholine and Alzheimer's Disease". Pristupljeno 24. 2. 2012.. *^ Stoelting R (1999). ... Nachmansohn, D. and Wilson, I.B. (1951). "The enzymic hydrolysis and synthesis of acetylcholine". Adv. Enzymol. Relat. Subj. ...
... 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. ...
"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 ...
... is a drug which acts as an agonist at neuronal nicotinic acetylcholine receptors being a full agonist of the α3β2 ... Identifying factors associated with alpha7 selectivity". Bioorganic & Medicinal Chemistry Letters. 13 (17): 2825-2828. doi: ... Cao, Y.; Surowy, C.; Puttfarcken, P. (2005). "Nicotinic acetylcholine receptor-mediated 3Hdopamine release from hippocampus". ... "Synthesis of two fluoro analogues of the nicotinic acetylcholine receptor agonist UB-165". The Journal of Organic Chemistry. 68 ...
... 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: ...
"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.[27] 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 ... receptor binding. • neurotrophin TRKB receptor binding. • growth factor activity. • GO:0001948 protein binding. ...
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: ...
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. ...
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 ...
... 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 ...
Seminar: Impact of alpha7 nicotinic acetylcholine receptors in amyloid-induced hyperpolarization and toxicity. 2013-09-2515:00 ...
Binding affinity of Norditerpenoid Alkaloids at rat neuronal alpha7-type nicotinic acetylcholine receptor. ...
Alpha7 nicotinic acetylcholine receptor (α7 nAChR) is a major cholinergic ligand-gated ion channel in the CNS, has been ... Zhang, B., Yu, J., Liu, L. et al. Alpha7 nicotinic acetylcholine receptor is required for blood-brain barrier injury-related ... Alpha7 nicotinic acetylcholine receptor is required for blood-brain barrier injury-related CNS disorders caused by Cryptococcus ... Recruitment of alpha7 nicotinic acetylcholine receptor to lipid rafts/caveolae is required for nicotine-enhanced Escherichia ...
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 ...
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 ...
The effect of crebanine on memory and cognition impairment via the alpha-7 nicotinic acetylcholine receptor. ... The molecular mechanism was explored in silico by docking crebanine against acetylcholine binding proteins (AChBPs) and in ... Image of a portion of a Xenopus oocyte expressing a channel receptor. ...
... 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 ...
The role of the alpha7 nicotinic acetylcholine receptor (α7nAChR) in inflammation has recently been identified. Our previous ... From: Downregulation of alpha7 nicotinic acetylcholine receptor in two-kidney one-clip hypertensive rats ...
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 ...
Results: Alpha7 nicotinic acetylcholine receptor, alpha7-nAChR, was identified in gastric cancer cell lines, AGS cells. ... Results: Alpha7 nicotinic acetylcholine receptor, alpha7-nAChR, was identified in gastric cancer cell lines, AGS cells. ... Results: Alpha7 nicotinic acetylcholine receptor, alpha7-nAChR, was identified in gastric cancer cell lines, AGS cells. ... Results: Alpha7 nicotinic acetylcholine receptor, alpha7-nAChR, was identified in gastric cancer cell lines, AGS cells. ...
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. ...
... ... 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 ( ...
Marked expression of the alpha7 nicotinic acetylcholine receptor (,i,α,/i,7nAChR) in the joint synovium of RA patients ... Marked expression of the alpha7 nicotinic acetylcholine receptor (α7nAChR) in the joint synovium of RA patients suggested a ... K. Tsoyi, H. J. Jang, J. W. Kim et al., "Stimulation of Alpha7 nicotinic acetylcholine receptor by nicotine attenuates ... W.-Y. Cui and M. D. Li, "Nicotinic modulation of innate immune pathways via α7 nicotinic acetylcholine receptor," Journal of ...
We tested the hypothesis whether the partially duplicated variant of alpha7 nicotinic acetylcholine receptor subunit gene ( ... Association between a genetic variant of the alpha-7 nicotinic acetylcholine receptor subunit and four types of dementia Agnes ... Association between a genetic variant of the alpha-7 nicotinic acetylcholine receptor subunit and four types of dementia Agnes ... We tested the hypothesis whether the partially duplicated variant of alpha7 nicotinic acetylcholine receptor subunit gene ( ...
Association with alpha7 nicotinic acetylcholine receptors. Am J Respir Cell Mol Biol. 2002;26(1):31-41pmid:11751201. ...
Receptors, Nicotinic * alpha7 Nicotinic Acetylcholine Receptor * Tryptophan Grant support * 5R25 GM 61151/GM/NIGMS NIH HHS/ ... Tryptophan substitutions reveal the role of nicotinic acetylcholine receptor alpha-TM3 domain in channel gating: differences ...
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 ...
Novel Alpha-7 Nicotinic Acetylcholine Receptor Agonists Containing a Urea Moiety: Identification and Characterization of the ...
Effect of alpha-7 nicotinic acetylcholine receptor activation on beta-amyloid induced recognition memory impairment. Possible ... Effect of alpha-7 nicotinic acetylcholine receptor activation on beta-amyloid induced reco ... α7-nAChR antagonist, methyllycaconitine (MLA) (1 mg/kg, i.p.), was used for evaluation of receptor blockade effects. ...
title = "Similarities between the binding sites of SB-206553 at serotonin type 2 and alpha7 acetylcholine nicotinic receptors: ... Similarities between the binding sites of SB-206553 at serotonin type 2 and alpha7 acetylcholine nicotinic receptors: Rationale ... Similarities between the binding sites of SB-206553 at serotonin type 2 and alpha7 acetylcholine nicotinic receptors: Rationale ... T1 - Similarities between the binding sites of SB-206553 at serotonin type 2 and alpha7 acetylcholine nicotinic receptors ...
... 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 ...
  • The selective alpha7 agonist GTS-21 attenuates cytokine production in human whole blood and human monocytes activated by ligands for TLR2, TLR3, TLR4, TLR9, and RAGE. (sigmaaldrich.com)
  • We tested the hypothesis whether the partially duplicated variant of alpha7 nicotinic acetylcholine receptor subunit gene (CHRFAM7A) 2-bp deletion (-2 bp) polymorphism and apolipoprotein E (ApoE) epsilon4 allele confer susceptibility to Alzheimer's disease (AD), dementia with Lewy bodies (DLB), Pick's disease (PiD) and vascular dementia (VD). (cdc.gov)
  • GTS-21 [3-(2,4-dimethoxybenzylidene) anabaseine], a selective alpha7 agonist, inhibits inflammatory cytokine production in murine and human macrophages and in several models of inflammatory disease in vivo, but to date its antiinflammatory efficacy in human monocytes has not been characterized. (sigmaaldrich.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)
  • 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)
  • In this week's PNAS Early Edition, Joachim Herz and colleagues at the University of Texas Southwestern Medical Center, Dallas, show that reelin signaling through apolipoprotein E (ApoE) receptors may support long-term potentiation (LTP) by counteracting Aβ-induced suppression of N-methyl-D-aspartate (NMDA) receptors. (alzforum.org)
  • Meanwhile, scientists had discovered that Aβ peptides can set in motion a molecular cascade resulting in the opposite effect on those same NMDA receptors. (alzforum.org)
  • All told, the data indicate that reelin and Aβ work against each other by triggering molecular cascades that have opposing effects on NMDA receptors. (alzforum.org)
  • We report here that the α7nAChR forms a protein complex with the NMDA glutamate receptor (NMDAR) through a direct protein-protein interaction. (rupress.org)
  • In addition, it was found that muscle-type receptors appeared to be somewhat more sensitive to R- (−)-mecamylamine than to S- (+)-mecamylamine. (aspetjournals.org)
  • Together, these findings suggest that in chronic (i.e., therapeutic) application, S- (+)-mecamylamine might be preferable to R- (−)-mecamylamine in terms of equilibrium inactivation of neuronal receptors with decreased side effects associated with muscle-type receptors. (aspetjournals.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)