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.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.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.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.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.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.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.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.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.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)Atropine: An alkaloid, originally from Atropa belladonna, but found in other plants, mainly SOLANACEAE. Hyoscyamine is the 3(S)-endo isomer of atropine.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.Physostigmine: 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.Neuromuscular Junction: The synapse between a neuron and a muscle.Carbachol: A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS.Tubocurarine: A neuromuscular blocker and active ingredient in CURARE; plant based alkaloid of Menispermaceae.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.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.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.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.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, 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.Vasodilation: The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.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.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.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)Vasodilator Agents: Drugs used to cause dilation of the blood vessels.Receptor, Muscarinic M3: A subclass of muscarinic receptor that mediates cholinergic-induced contraction in a variety of SMOOTH MUSCLES.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.Motor 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.Muscles: Contractile tissue that produces movement in animals.Mecamylamine: 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.Choline O-Acetyltransferase: An enzyme that catalyzes the formation of acetylcholine from acetyl-CoA and choline. EC 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.Nitroprusside: A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.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)Cholinergic Agonists: Drugs that bind to and activate cholinergic receptors.AzocinesParasympatholytics: Agents that inhibit the actions of the parasympathetic nervous system. The major group of drugs used therapeutically for this purpose is the MUSCARINIC ANTAGONISTS.Oxotremorine: A non-hydrolyzed muscarinic agonist used as a research tool.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.Guinea Pigs: A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.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.Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.Quinuclidinyl Benzilate: A high-affinity muscarinic antagonist commonly used as a tool in animal and tissue studies.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.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).Cholinergic Fibers: Nerve fibers liberating acetylcholine at the synapse after an impulse.Hexamethonium Compounds: Compounds containing the hexamethylenebis(trimethylammonium) cation. Members of this group frequently act as antihypertensive agents and selective ganglionic blocking agents.Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.N-Methylscopolamine: A muscarinic antagonist used to study binding characteristics of muscarinic cholinergic receptors.Electric Stimulation: Use of electric potential or currents to elicit biological responses.Hemicholinium 3: A potent inhibitor of the high affinity uptake system for CHOLINE. It has less effect on the low affinity uptake system. Since choline is one of the components of ACETYLCHOLINE, treatment with hemicholinium can deplete acetylcholine from cholinergic terminals. Hemicholinium 3 is commonly used as a research tool in animal and in vitro experiments.Dihydro-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.Cholinergic Antagonists: Drugs that bind to but do not activate CHOLINERGIC RECEPTORS, thereby blocking the actions of ACETYLCHOLINE or cholinergic agonists.Muscle Denervation: The resection or removal of the innervation of a muscle or muscle tissue.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)Scopolamine Hydrobromide: An alkaloid from SOLANACEAE, especially DATURA and SCOPOLIA. Scopolamine and its quaternary derivatives act as antimuscarinics like ATROPINE, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in URINARY INCONTINENCE, in MOTION SICKNESS, as an antispasmodic, and as a mydriatic and cycloplegic.Neostigmine: A cholinesterase inhibitor used in the treatment of myasthenia gravis and to reverse the effects of muscle relaxants such as gallamine and tubocurarine. Neostigmine, unlike PHYSOSTIGMINE, does not cross the blood-brain barrier.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.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.Muscle, Smooth: Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)QuinolizinesGallamine 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)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.Iontophoresis: Therapeutic introduction of ions of soluble salts into tissues by means of electric current. In medical literature it is commonly used to indicate the process of increasing the penetration of drugs into surface tissues by the application of electric current. It has nothing to do with ION EXCHANGE; AIR IONIZATION nor PHONOPHORESIS, none of which requires current.Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.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.Decamethonium Compounds: Compounds that contain the decamethylenebis(trimethyl)ammonium radical. These compounds frequently act as neuromuscular depolarizing agents.Pirenzepine: An antimuscarinic agent that inhibits gastric secretion at lower doses than are required to affect gastrointestinal motility, salivary, central nervous system, cardiovascular, ocular, and urinary function. It promotes the healing of duodenal ulcers and due to its cytoprotective action is beneficial in the prevention of duodenal ulcer recurrence. It also potentiates the effect of other antiulcer agents such as CIMETIDINE and RANITIDINE. It is generally well tolerated by patients.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.Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.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.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.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.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.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.Ileum: The distal and narrowest portion of the SMALL INTESTINE, between the JEJUNUM and the ILEOCECAL VALVE of the LARGE INTESTINE.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.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.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.Muscarine: A toxic alkaloid found in Amanita muscaria (fly fungus) and other fungi of the Inocybe species. It is the first parasympathomimetic substance ever studied and causes profound parasympathetic activation that may end in convulsions and death. The specific antidote is atropine.Muscle Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position.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.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.Myasthenic 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)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.Kinetics: The rate dynamics in chemical or physical systems.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.Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane.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.Potassium: An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.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.CholinesterasesNerve Endings: Branch-like terminations of NERVE FIBERS, sensory or motor NEURONS. Endings of sensory neurons are the beginnings of afferent pathway to the CENTRAL NERVOUS SYSTEM. Endings of motor neurons are the terminals of axons at the muscle cells. Nerve endings which release neurotransmitters are called PRESYNAPTIC TERMINALS.Piperidines: A family of hexahydropyridines.Biological Factors: Endogenously-synthesized compounds that influence biological processes not otherwise classified under ENZYMES; HORMONES or HORMONE ANTAGONISTS.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).Forearm: Part of the arm in humans and primates extending from the ELBOW to the WRIST.Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Receptor Aggregation: Chemically stimulated aggregation of cell surface receptors, which potentiates the action of the effector cell.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.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.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.Diaphragm: The musculofibrous partition that separates the THORACIC CAVITY from the ABDOMINAL CAVITY. Contraction of the diaphragm increases the volume of the thoracic cavity aiding A competitive inhibitor of nitric oxide synthetase.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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.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.Action Potentials: Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.Vasoconstriction: The physiological narrowing of BLOOD VESSELS by contraction of the VASCULAR SMOOTH MUSCLE.Cholinergic Neurons: Neurons whose primary neurotransmitter is ACETYLCHOLINE.Nitroarginine: An inhibitor of nitric oxide synthetase which has been shown to prevent glutamate toxicity. Nitroarginine has been experimentally tested for its ability to prevent ammonia toxicity and ammonia-induced alterations in brain energy and ammonia metabolites. (Neurochem Res 1995:200(4):451-6)Methacholine Compounds: A group of compounds that are derivatives of beta-methylacetylcholine (methacholine).Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Vasoconstrictor Agents: Drugs used to cause constriction of the blood vessels.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.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.Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.Histamine: An amine derived by enzymatic decarboxylation of HISTIDINE. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter.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.Neuromuscular Depolarizing Agents: Drugs that interrupt transmission at the skeletal neuromuscular junction by causing sustained depolarization of the motor end plate. These agents are primarily used as adjuvants in surgical anesthesia to cause skeletal muscle relaxation.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Bradykinin: A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter.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.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.Cats: The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801)Quaternary 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.Xenopus: An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.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.Snakes: Limbless REPTILES of the suborder Serpentes.Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi.Anabasine: A piperidine botanical insecticide.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.Nitroglycerin: A volatile vasodilator which relieves ANGINA PECTORIS by stimulating GUANYLATE CYCLASE and lowering cytosolic calcium. It is also sometimes used for TOCOLYSIS and explosives.Mesenteric Arteries: Arteries which arise from the abdominal aorta and distribute to most of the intestines.Proadifen: An inhibitor of drug metabolism and CYTOCHROME P-450 ENZYME SYSTEM activity.Vasomotor System: The neural systems which act on VASCULAR SMOOTH MUSCLE to control blood vessel diameter. The major neural control is through the sympathetic nervous system.Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx).Ganglionic Blockers: Agents having as their major action the interruption of neural transmission at nicotinic receptors on postganglionic autonomic neurons. Because their actions are so broad, including blocking of sympathetic and parasympathetic systems, their therapeutic use has been largely supplanted by more specific drugs. They may still be used in the control of blood pressure in patients with acute dissecting aortic aneurysm and for the induction of hypotension in surgery.Potassium Chloride: A white crystal or crystalline powder used in BUFFERS; FERTILIZERS; and EXPLOSIVES. It can be used to replenish ELECTROLYTES and restore WATER-ELECTROLYTE BALANCE in treating HYPOKALEMIA.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)Myenteric Plexus: One of two ganglionated neural networks which together form the ENTERIC NERVOUS SYSTEM. The myenteric (Auerbach's) plexus is located between the longitudinal and circular muscle layers of the gut. Its neurons project to the circular muscle, to other myenteric ganglia, to submucosal ganglia, or directly to the epithelium, and play an important role in regulating and patterning gut motility. (From FASEB J 1989;3:127-38)Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.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)Nitric Oxide Synthase: An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.Paraoxon: An organophosphate cholinesterase inhibitor that is used as a pesticide.AzetidinesAorta, Thoracic: The portion of the descending aorta proceeding from the arch of the aorta and extending to the DIAPHRAGM, eventually connecting to the ABDOMINAL AORTA.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).NG-Nitroarginine Methyl Ester: A non-selective inhibitor of nitric oxide synthase. It has been used experimentally to induce hypertension.Rana pipiens: A highly variable species of the family Ranidae in Canada, the United States and Central America. It is the most widely used Anuran in biomedical research.Arginine: An essential amino acid that is physiologically active in the L-form.Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes.TritiumDrug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.QuinuclidinesCell Line: Established cell cultures that have the potential to propagate indefinitely.Phenylephrine: An alpha-1 adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent.Coronary Vessels: The veins and arteries of the HEART.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.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.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.Electric Conductivity: The ability of a substrate to allow the passage of ELECTRONS.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.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)Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Regional Blood Flow: The flow of BLOOD through or around an organ or region of the body.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.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.Muscle, Smooth, Vascular: The nonstriated involuntary muscle tissue of blood vessels.Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of PAIN, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses.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.Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries.Sweat Glands: Sweat-producing structures that are embedded in the DERMIS. Each gland consists of a single tube, a coiled body, and a superficial duct.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.Cerebral Cortex: The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulchi. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.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)Coronary Vasospasm: Spasm of the large- or medium-sized coronary arteries.Ganglia, Sympathetic: Ganglia of the sympathetic nervous system including the paravertebral and the prevertebral ganglia. Among these are the sympathetic chain ganglia, the superior, middle, and inferior cervical ganglia, and the aorticorenal, celiac, and stellate ganglia.Benzylidene Compounds: Compounds containing the PhCH= radical.QuinoxalinesRats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Anura: An order of the class Amphibia, which includes several families of frogs and toads. They are characterized by well developed hind limbs adapted for jumping, fused head and trunk and webbed toes. The term "toad" is ambiguous and is properly applied only to the family Bufonidae.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.Isoproterenol: Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.Catecholamines: A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine.gamma-Aminobutyric Acid: The most common inhibitory neurotransmitter in the central nervous system.Fishes: A group of cold-blooded, aquatic vertebrates having gills, fins, a cartilaginous or bony endoskeleton, and elongated bodies covered with scales.Motor Neurons: Neurons which activate MUSCLE CELLS.Arecoline: An alkaloid obtained from the betel nut (Areca catechu), fruit of a palm tree. It is an agonist at both muscarinic and nicotinic acetylcholine receptors. It is used in the form of various salts as a ganglionic stimulant, a parasympathomimetic, and a vermifuge, especially in veterinary practice. It has been used as a euphoriant in the Pacific Islands.Pilocarpine: A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma.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.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.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.Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016).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.Stimulation, Chemical: The increase in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical.