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.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.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.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.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)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.AzocinesBicyclo 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)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.QuinolizinesAzetidinesCholinergic 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.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.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.Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.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.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.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.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.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.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.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.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.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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.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.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.Anabasine: A piperidine botanical insecticide.Saimiri: A genus of the family CEBIDAE consisting of four species: S. boliviensis, S. orstedii (red-backed squirrel monkey), S. sciureus (common squirrel monkey), and S. ustus. They inhabit tropical rain forests in Central and South America. S. sciureus is used extensively in research studies.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).Tobacco Use Disorder: Tobacco used to the detriment of a person's health or social functioning. Tobacco dependence is included.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.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.QuinoxalinesGanglionic 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.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.Drug Partial Agonism: Drug agonism involving selective binding but reduced effect. This can result in some degree of DRUG ANTAGONISM.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.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)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.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.Benzazepines: Compounds with BENZENE fused to AZEPINES.Superior Cervical Ganglion: The largest and uppermost of the paravertebral sympathetic ganglia.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.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).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.Morantel: Antinematodal agent used mainly for livestock.Phenylurea Compounds: Compounds that include the amino-N-phenylamide structure.Cholinergic Agonists: Drugs that bind to and activate cholinergic receptors.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.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.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.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)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.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.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.Excitatory Postsynaptic Potentials: Depolarization of membrane potentials at the SYNAPTIC MEMBRANES of target neurons during neurotransmission. Excitatory postsynaptic potentials can singly or in summation reach the trigger threshold for ACTION POTENTIALS.Mice, Inbred C57BLBicyclo CompoundsMembrane 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).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.Benzylidene Compounds: Compounds containing the PhCH= radical.Picolines: A group of compounds that are monomethyl derivatives of pyridines. (From Dorland, 28th ed)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.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.CA1 Region, Hippocampal: One of four subsections of the hippocampus described by Lorente de No, located furthest from the DENTATE GYRUS.Xenopus: An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.Cholinergic Antagonists: Drugs that bind to but do not activate CHOLINERGIC RECEPTORS, thereby blocking the actions of ACETYLCHOLINE or cholinergic agonists.Receptors, Presynaptic: Neurotransmitter receptors located on or near presynaptic terminals or varicosities. Presynaptic receptors which bind transmitter molecules released by the terminal itself are termed AUTORECEPTORS.Kynurenic Acid: A broad-spectrum excitatory amino acid antagonist used as a research tool.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.
... nAChRs), the kappa-bungarotoxin family with neuronal nAChRs, and muscarinic toxins with muscarinic acetylcholine receptors ( ... Alpha-bungarotoxin, the alpha-neurotoxin from the many-banded krait (Bungarus multicinctus), has a long history of use in ... The kappa-bungarotoxin group is the best characterized dimeric 3FTx, and interacts through an antiparallel dimer interface ... In general, short-chain 3FTx members of this group bind muscle nAChRs only, and long-chain members bind both muscle and ...
For example, α-bungarotoxin is specific for nAChRs found in the musculature and κ-bungarotoxin is specific for nAChRs found in ... As there are multiple forms of bungarotoxin, there are different forms of nAChRs to which they will bind, and α-bungarotoxin is ... Bungarotoxin is a compound with known interaction with nicotinic acetylcholine receptors (nAChRs), which constitute a family of ... Additionally, different forms of bungarotoxin may be useful for studying inhibited nAChRs and their resultant calcium ion flow ...
... nAChRs) with a Ki ~1 x 10−6M. Similar experiments performed later by Ward et al. showed that MLA bound to nAChRs extracted from ... When compared in nAChR-binding studies, MLA was found to compete for 125I-α-bungarotoxin binding sites (i.e. α7 sub-types) over ... Further details about the binding of MLA to nAChRs were presented by Wonnacott and her co-workers, who provided evidence that ... Subsequently, Macallan and his co-workers showed that MLA also competed with 125I-α-bungarotoxin (Ki ~1 x 10−9M) and tritiated ...
Alpha-Bungarotoxin and nicotinic acetylcholine receptor α-Neurotoxins antagonistically bind tightly and noncovalently to nAChRs ... nAChRs contain two binding sites for snake venom neurotoxins. Progress towards discovering the dynamics of binding action of ... The term α-neurotoxin was coined by C.C. Chang, who designated the postsynaptic bungarotoxin with the α- prefix because it ... α-Neurotoxins from snake venoms that tightly bind nAChRs contain 60-75 amino acid (aa) residues and are linked by 4-5 disulfide ...
In neuronal nAChRs, the binding site is located at the interface of an α and a β subunit or between two α subunits in the case ... and that one or two molecules of α-bungarotoxin (or other long-chain α-neurotoxin) suffice to halt this motion. The toxins seem ... In muscle-type nAChRs, the acetylcholine binding sites are located at the α and either ε or δ subunits interface. ... As ionotropic receptors, nAChRs are directly linked to ion channels. New evidence suggests that these receptors can also use ...
nAChRs contain two binding sites for snake venom neurotoxins. Progress towards elucidation of the dynamics of binding action of ... Beta-bungarotoxin Kappa-bungarotoxin Young, Howard S.; Herbette, Leo G.; Skita, Victor (August 2003). "α-Bungarotoxin Binding ... α-Bungarotoxin (α-BTX) is one of the bungarotoxins, components of the venom of the elapid snake the Taiwanese banded krait ( ... α-Bungarotoxin is a 74-amino-acid, 8 kDa α-neurotoxin with five disulfide bridges that binds as a competitive antagonist to ...
... is a high affinity antagonist of nicotinic acetylcholine receptors (nAChRs), particularly of CHRNA3; it ... "bungarotoxin 3.1" were identified by protein sequencing as identical to kappa-bungarotoxin. Kappa-bungarotoxin binds to the ... Like the alpha-bungarotoxins, kappa-bungarotoxin causes a post-synaptic blockade of signaling; this is in contrast to the beta- ... Kappa-bungarotoxin (often written κ-Bgt; historically also called toxin F) is a protein neurotoxin of the bungarotoxin family ...
... nAChRs) are members of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. The nAChRs ... alpha-bungarotoxin. Once this receptor binds acetylcholine, it undergoes an extensive change in conformation that affects all ...
α4β2 nAChRs account for approximately 90% of the nAChRs in the human brain and when chronically exposed to nicotine or other ... have as much affinity for nicotine as the heteromeric receptor but instead they have shown more affinity for alpha bungarotoxin ... There are two binding sites on heteromeric nAChRs; to stabilize the open form of nAChRs, both binding sites must be occupied by ... The nAChRs found in the skeletal muscle system have two ACh binding sites, one of which is found at the interface between α1 ...
... nAChRs) on the cell membrane of the muscle fiber, also known as the sarcolemma. nAChRs are ionotropic receptors, meaning they ... α-Bungarotoxin is a toxin found in the snake species Bungarus multicinctus that acts as an ACh antagonist and binds to AChRs ... to the α-bungarotoxin, AChRs can be visualized and quantified. Nerve gases and liquor damage this area. Botulinum toxin (aka ... nAChRs) at the neuromuscular junction. With this technique, a microelectrode was placed inside the motor endplate of the muscle ...
The nAChRs are thought to be (hetero)pentamers composed of homologous subunits. Click on genes, proteins and metabolites below ... Chini B, Clementi F, Hukovic N, Sher E (1992). "Neuronal-type alpha-bungarotoxin receptors and the alpha 5-nicotinic receptor ... nAChRs), such as CHRNA5, are members of a superfamily of ligand-gated ion channels that mediate fast signal transmission at ...
2002). "How mutations in the nAChRs can cause ADNFLE epilepsy". Epilepsia. 43 Suppl 5: 112-22. doi:10.1046/j.1528-1157.43.s. ... "Identification of a brain acetylcholine receptor alpha subunit able to bind alpha-bungarotoxin". J. Biol. Chem. 265 (17): 9816- ... nAChRs) are members of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. After ...
The nAChRs are ligand-gated ion channels, and, like other members of the "cys-loop" ligand-gated ion channel superfamily, are ... like α-bungarotoxin. Drugs such as the neuromuscular blocking agents bind reversibly to the nicotinic receptors in the ...
α-Neurotoxins (e.g., α-bungarotoxin, α-cobratoxin, α-conotoxin, many others) ...
α-Neurotoxins (e.g., α-bungarotoxin, α-cobratoxin, α-conotoxin, many others) ...
α-Neurotoxins (e.g., α-bungarotoxin, α-cobratoxin, α-conotoxin, many others) ... nAChRs. Agonists. (and PAMs). *5-HIAA. *A-84,543. *A-366,833. *A-582,941 ...
Kappa-bungarotoxin is a high affinity antagonist of nicotinic acetylcholine receptors (nAChRs), particularly of CHRNA3; it ... "bungarotoxin 3.1" were identified by protein sequencing as identical to kappa-bungarotoxin. Kappa-bungarotoxin binds to the ... Like the alpha-bungarotoxins, kappa-bungarotoxin causes a post-synaptic blockade of signaling; this is in contrast to the beta- ... Kappa-bungarotoxin (often written κ-Bgt; historically also called toxin F) is a protein neurotoxin of the bungarotoxin family ...
... of nicotine against kainic acid excitotoxicity is associated with alpha-bungarotoxin insensitive receptors subtype of nAChRs.. ... Journal Article 2011; 32(6): 816-820 PubMed PMID: 22286796 Keywords: Animals, Bungarotoxins:metabolism, Excitatory Amino Acid ... of nicotine against kainic acid excitotoxicity is associated with alpha-bungarotoxin insensitive receptors subtype of nAChRs. ...
These were stained for nAChRs, Cav-1 and nuclei with α-bungarotoxin, immunohistochemistry using anti-Cav-1 antibodies and DAPI ...
... sensitivity to neuronal bungarotoxin was interpreted in favor of α3-containing nAChRs (Grady et al., 1992). These disparate ... Upregulation of α4β2 nAChRs. (±)-Epibatidine and (±)-anatoxin-a differ in their abilities to upregulate α4β2 nAChRs in the M10 ... The weak partial agonism of UB-165 at α4β2* nAChRs contrasts with its full efficacy in upregulating α4β2 nAChRs in M10 cells ( ... or homo-oligomeric nAChRs of α7 subunits (Fig.6). (±)-UB-165 was most potent in activating α4β4 and α2β4 nAChRs (EC50 = 0.05 μm ...
Epibatidine is a potent agonist of heteromeric nAChRs, while -α-bungarotoxin (α-Bgt) binds to both muscle-type nAChRs and ... The presence of nAChRs in B lymphocytes was further confirmed by studying the [3H]-epibatidine and [125I]-α-bungarotoxin ... The first is a class with [125I]-α-bungarotoxin ([125I]-α-bgt) binding sites specific to homomeric α7 nAChRs. The second is a ... α-Bungarotoxin binding sites were found in both smokers and non-smokers leukocytes, such as PMN, and thus can serve as an ...
IP/Western blot shows the inhibition of the Rb-Raf-1 interaction by α7-nAChRs inhibitors α-bungarotoxin and MAA. (E) Penetratin ... F) The binding of β-arrestin to nAChRs seen in E was confirmed by IP using β-nAChR antibody and Western blotting for β-arrestin ... E) Nicotine induced the binding of c-Src to β-nAChRs. Quiescent A549 cells were stimulated with 1 μM nicotine for 15 or 30 ... F) The binding between c-Src and nAChRs was inhibited by the Src inhibitor PP2. Quiescent A549 cells were stimulated by 1 μM ...
Functional nAChRs that have the pharmacological properties of α3-containing nAChRs have been found in glutamatergic neurons/ ... α- bungarotoxin. ACSF. artificial cerebrospinal fluid. ANOVA. analysis of variance. APV. 2-amino-5-phosphonovaleric acid. CNQX ... 2 and 3) may be caused by the ability of MLA to block some heteromeric α7 or non-α7 nAChRs. The α7 nAChR currents in ... Alternatively, some of the MLA effects may arise from blockade of non-α7 heteromers such as α4α6α5(β2)2 or α3α4α5(β2)2 nAChRs, ...
... nAChRs), the kappa-bungarotoxin family with neuronal nAChRs, and muscarinic toxins with muscarinic acetylcholine receptors ( ... Alpha-bungarotoxin, the alpha-neurotoxin from the many-banded krait (Bungarus multicinctus), has a long history of use in ... The kappa-bungarotoxin group is the best characterized dimeric 3FTx, and interacts through an antiparallel dimer interface ... In general, short-chain 3FTx members of this group bind muscle nAChRs only, and long-chain members bind both muscle and ...
... bungarotoxin and neuronal bungarotoxin. In contrast, nAChRs recorded on the soma of MHB neurons under equivalent experimental ... The action of nicotine was insensitive to alpha-bungarotoxin and to neuronal bungarotoxin, but was blocked by mecamylamine, ... nAChRs located on the soma of IPN neurons were studied using patch-clamp techniques and a preparation of acutely isolated ... The pharmacological properties of presynaptic nAChRs in the IPN were analyzed in a rat brain slice preparation. Stimulation of ...
α-bungarotoxin is a snake venom neurotoxin that acts as an antagonist at nicotinic acetylcholine receptors (nAChRs). This ... 125I]-Tyr54-, High Specific Activity" data-title=α-Bungarotoxin, [125I]-Tyr54-, High Specific Activity class="a_dblue"> α- ... α-bungarotoxin, labeled with 125I on tyrosine residue 54. ... Bungarotoxin, [125I]-Tyr54-, High Specific Activity 125I]-Tyr54 ...
NNK and NNN are agonists for α-bungarotoxin α7 nAChR and the heteromeric, epibatidine-sensitive α-β nAChRs, respectively (20). ... Second, nAChRs that are functionally present in human lung airway epithelial cells and in lung carcinomas may play a direct, ... The long internal loop of the α 3 subunit targets nAChRs to subdomains within individual synapses on neurons in vivo. Nat ... whereas the affinity of NNN for heteromeric α-β nAChRs was 5,000 times higher than that of nicotine (20, 21). Recent studies ...
Many small molecules interact with nAChRs including d-tubocurarine, snake venom protein α-bungarotoxin (α-Bgt), and α- ... Various more recently discovered compounds of different structural classes also interact with nAChRs including the low- ... Dimethylaniline mimics the low potency and non-competitive actions of lidocaine on nAChRs, as opposed to the high potency and ...
Synaptophysin and neurofilament 200 (red color) and α-bungarotoxin (BTX, green color) were used to label motor nerve terminals ... The morphology of NMJs including motor nerve terminals and nAChRs located on gastrocnemius muscles from all experimental groups ... 488 labeled α-Bungarotoxin (α-BTX, Thermo Fisher Scientific, Waltham, MA). Finally, images of muscle segments mounted on glass ...
It was further experimentally confirmed via competition with radioiodinated α-bungarotoxin ([125I]-αBgt) for binding to AChBP ... 359 and aaptamine showed inhibitory activities in electrophysiology experiments on the mouse muscle and human α7 nAChRs, ... nAChRs), was carried out and the possibility of complex formation was revealed. ... It was further experimentally confirmed via competition with radioiodinated α-bungarotoxin ([125I]-αBgt) for binding to AChBP ...
... an effect mediated by α-bungarotoxin-sensitive nAChRs. By using different genetic tools we demonstrate that the BA whose efflux ... Nicotine activates alpha-bungarotoxin-sensitive nAChRs, causing a rapid increase in intracellular calcium levels in over 95% of ... For instance, it is not known whether the activation of nicotinic acetylcholine receptors (nAChRs) induces the release of BAs ... These data demonstrate that activation of nAChRs induces a calcium-dependent plasticity in Kenyon cells that could contribute ...
... nAChRs) of muscle and neuronal (α7) types was... ... nAChRs) of muscle and neuronal (α7) types was studied by ... competitive radioligand assay with the use of 125I-α-bungarotoxin. The resulting peptides exhibited a significantly greater ... binding activity with respect to the muscle-type nAChRs than to the α7 receptor. Thus, we have discovered a new class of nAChR ...
Fluorescent α-Bungarotoxins. Nicotinic acetylcholine receptors (nAChRs) are neurotransmitter-gated ion channels that produce an ... Biotinylated α-Bungarotoxin. Nicotinic AChRs can also be labeled with biotinylated α-bungarotoxin (B1196), which is then ... Unlabeled α-Bungarotoxin. In addition to the fluorescent and biotinylated derivatives, we have unlabeled α-bungarotoxin (B1601 ... Alexa Fluor 488 α-bungarotoxin (B13422) has fluorescence spectra similar to those of fluorescein α-bungarotoxin (F1176) and is ...
Thus, alpha7 nAChRs could be involved in a form of cholinergically mediated excitotoxicity following brain injury. In the ... bungarotoxin (BTX) binding. We have postulated that deficits in alpha7 expression may contribute to TBI-induced cognitive ...
The ability of alpha7 nAChRs to promote the phosphorylation of presynaptic ERK2 and synapsin-1, downstream of CICR, provides a ... The alpha7 nAChR ligand alpha-bungarotoxin and ryanodine receptors were colocalized to a subpopulation of PFC synaptosomes. ... The ability of alpha7 nAChRs to promote the phosphorylation of presynaptic ERK2 and synapsin-1, downstream of CICR, provides a ... Activation of both alpha7 and beta2(*) nicotinic acetylcholine receptors (nAChRs) in the prefrontal cortex (PFC) has been ...
The discovery of the archetypal α-bungarotoxin (α-BgTx), almost six decades ago, exponentially expanded our knowledge of ... nAChRs) at the neuromuscular junction (NMJ) to produce skeletal muscle paralysis. ...
... which by raising ACh levels throughout the brain will also affect all nAChRs. In another study, ɑ-bungarotoxin, a specific ... The targets of neonicotinoid pesticides, nAChRs, play an important role in honey bee learning and memory processes vital to ... 2006). Involvement of alpha-bungarotoxin-sensitive nicotinic receptors in long-term memory formation in the honeybee (Apis ... nAChRs) (Buckingham et al., 1997; Elbert et al., 2008; Ihara et al., 2006). Unfortunately, because they are systemic ...
Crotoxin competed with radioactive α-bungarotoxin for binding to Torpedo and human α7 nAChRs and to the acetylcholine binding ... It was found that porcine pancreatic PLA2 and presynaptic -bungarotoxin blocked currents mediated by nAChRs in Lymnaea neurons ... and to compete with α-bungarotoxin for binding to nicotinic acetylcholine receptors (nAChRs) and acetylcholine binding protein ... Since nAChRs are implicated in postsynaptic and presynaptic activities, in this work we probe those PLA2s known to have strong ...
... nAChRs exist in these neurons because nicotine-induced currents can be suppressed by the α7-selective antagonist α-bungarotoxin ... Thus, α7 nAChRs represent a candidate subtype of nAChRs that could play a role in the local regulation of heart rate. ... 1A). Because cytisine is thought to act as a full agonist at nAChRs containing β4 subunits, our results suggest that the nAChRs ... which is a full agonist at β4-containing nAChRs but only a partial agonist at β2-containing nAChRs (Luetje and Patrick, 1991; ...
Modeling and molecular dynamic studies indicated that α-Ctx or α-bungarotoxin seem to interact with GABAAR in a way similar to ... It was found that BMLCL is able to interact with high efficiency with both α7 and muscle type nAChRs.. ... This result agrees with the earlier demonstrated competition of ws-Lynx1 with radioiodinated α-bungarotoxin for binding to ... 0 (BMLCL protein, Bungarus multicinctus multicinctus); 0 (Bungarotoxins); 0 (Cholinergic Agents); 0 (Cobra Neurotoxin Proteins ...
... pharmacological evidence using 125I-labeled α-bungarotoxin and [3H] nicotine to differentiate subtypes of nAChRs affinities ... Several modulators of nAChRs have been tested against schizophrenia. For example, a partial agonist of the α7 nAChR, DMXB-A ( ... It has been suggested that α7 nAChRs is not the main target of cotinine (Riah et al., 1999) and other type of receptors for ... The effects of PNU-120596 in vitro were shown to be mediated by α7 nAChRs. As a positive allosteric modulator, PNU-120596 ...
  • 3 H]Tetracaine binds at equilibrium to a single site with a K eq value of 0.5 μM in the absence of agonist or presence of α-bungarotoxin and with a K eq value of 30 μM in the presence of agonist (i.e., for nAChR in the desensitized state). (aspetjournals.org)
  • Because choline is a partial agonist for α3β4 nAChRs (Alkondon et al. (cambridge.org)
  • The structure of the muscle-type (from Torpedo electric organs) nAChR has been resolved to 4 Ǻ by electron microscopy, whereas insight into the extracellular domain and agonist binding site of nAChRs has come from the X-ray crystal structure (resolution down to 2.7 Ǻ) of a molluscan ACh binding protein. (sigmaaldrich.com)
  • GTS-21 is a partial agonist at α7 nAChR, with reported cognition enhancing activity, while AR-R 17779 is a full agonist at α7 nAChRs. (sigmaaldrich.com)
  • The non-alpha 7 nAChR agonist 5-Iodo-A-85380 produces alpha-bungarotoxin-insensitive increases in intracellular Ca2+ (EC50 11.2 mu M). Using these selective agonists or KCl in conjunction with general and selective VOCC inhibitors, we demonstrate that the primary route of Ca2+ entry following either non-alpha 7 nAChR activation or KCl stimulation is via L-type VOCCs. (bath.ac.uk)
  • Thus, alpha7 nAChRs could be involved in a form of cholinergically mediated excitotoxicity following brain injury. (eurekamag.com)
  • Using the alpha7 and beta2(*) nAChR-selective agonists (R)-N-(1-azabicyclo[2.2.oct-3-yl)(5-(2-pyridyl)thiophene-2-carboxamide) (compound A) and 5-iodo-3-(2(S)-azetidinylmethoxy)pyridine (5-iodo-A-85380), respectively, in conjunction with inhibitors of voltage-operated Ca(2+) channels (VOCCs) and intracellular Ca(2+) stores, we show that [(3)H]d-aspartate release evoked by activation of beta2(*) nAChRs occurs via VOCCs. (unboundmedicine.com)
  • The ability of alpha7 nAChRs to promote the phosphorylation of presynaptic ERK2 and synapsin-1, downstream of CICR, provides a potential mechanism for presynaptic facilitation in the PFC. (unboundmedicine.com)
  • The research will focus on the alpha7 neuronal nAChR because they are localized at presynaptic terminals and are sensitive to a-bungarotoxin, suggesting their importance in regulating neurotransmitter release. (grantome.com)
  • Alpha7 nAChRs will be reconstituted from oocyte surface membranes into planar lipid bilayer where we can control the ionic and regulatory environment of the channels. (grantome.com)
  • The resulting peptides exhibited a significantly greater binding activity with respect to the muscle-type nAChRs than to the α7 receptor. (springer.com)
  • Other studies report that Aβ interaction with nAChRs leads to receptor antagonism, indicating that the precise location and conditions under which receptor-peptide interaction takes place can lead to quite varied outcomes. (alzforum.org)
  • A mutation of the GPBC in the α7 nAChR (α7345-348A) abolishes interaction with Gαq as well as Gβγ while having no effect on receptor synthesis, cell-surface trafficking, or α-bungarotoxin binding. (wingsforlife.com)
  • For example, with regards to various disease states, nAChRs have for some time now been studied in an attempt to find a possible nexus between targeting of the receptor and treatment of small cell lung carcinoma (SCLC). (justia.com)
  • The adapted in vitro radioligand competition assays using [(3)H]epibatidine and [(125)I]bungarotoxin against the AChBPs from the marine species, Aplysia californica (Ac), and from the freshwater snails, Lymnaea stagnalis (Ls) and Bolinus truncates (Bt), revealed 4 compounds from the list of inhibitor candidates that had micromolar to nanomolar interferences for the toxin binding to AChBPs. (nih.gov)
  • The 3-pyridyl ether A-85380 was designed to discriminate central and peripheral nAChRs, and can also distinguish subpopulations of [ 3 H]epibatidine binding sites in brain membranes. (sigmaaldrich.com)
  • NACHO knockout mice show profound deficits in binding sites for α-bungarotoxin, epibatidine, and conotoxin MII, illustrating essential roles for NACHO in proper assembly of α7-, α4β2-, and α6-containing nAChRs, respectively. (viewpoint.fr)
  • 2005, 48, 4705) Nevertheless, subtype-selective antagonists may possess intrinsic value as tools to define the roles played by α7 nAChRs in the physiological and pathophysiological processes. (justia.com)
  • historically also called toxin F) is a protein neurotoxin of the bungarotoxin family that is found in the venom of the many-banded krait, a snake found in Taiwan. (wikipedia.org)
  • Separately identified toxins designated "toxin F" and "bungarotoxin 3.1" were identified by protein sequencing as identical to kappa-bungarotoxin. (wikipedia.org)
  • For example, the krait Bungarus multicinctus derived peptide toxin α-bungarotoxin (α-BTX) and the seeds of Delphinum isolated nonpetide toxin methyllycaconitine (MLA) are two frequently used α7 selective antagonists. (justia.com)
  • These differences indicate that the cell population, subcellular location, accessory proteins, and posttranslational modifications may influence the net effect of Aβ on nAChRs. (alzforum.org)
  • In recent studies we show that α7 nAChRs bind signaling proteins such as heterotrimeric GTP-binding proteins (G proteins). (wingsforlife.com)
  • Here, we demonstrate that direct coupling of α7 nAChRs to G proteins enables a downstream calcium signaling response that can persist beyond the expected time course of channel activation. (wingsforlife.com)
  • nAChRs are pentameric transmembrane proteins that form cationic channels permeable to Na + , K + , and Ca 2+ . (sigmaaldrich.com)
  • In this study, we identified proteins that associate with α7-nAChRs when Ric-3 is expressed. (barrowneuro.org)
  • Using α-bungarotoxin (α-bgtx), we isolated and compared α7-nAChR-associated proteins from two stably transfected, human tumor-derived cell lines: SH-EP1-hα7 expressing human α7-nAChRs and the same cell line further transfected to express Ric-3, SH-EP1- hα7-Ric-3. (barrowneuro.org)
  • Mass spectrometric analysis of peptides identified thirty-nine proteins that are associated with α7-nAChRs only when Ric-3 was expressed. (barrowneuro.org)
  • These results illuminate how α-bgtx may be used to isolate and identify α7-nAChRs as well as how the expression of chaperones such as Ric-3 can influence proteins associating with α7-nAChRs. (barrowneuro.org)
  • These associating proteins may alter activities of α7-nAChRs to expand their functionally-relevant repertoire as well as to affect biogenesis and membrane trafficking of α7-nAChRs. (barrowneuro.org)
  • The in vitro synthesized nAChRs will be reconstituted into planar lipid bilayers to characterize their functional properties in the absence of other membrane proteins that may act as allosteric regulators. (grantome.com)
  • A detailed investigation of the carcinogenic effects of nAChRs and their specific antagonists would enhance our understanding of their value as targets for clinical translation. (aacrjournals.org)
  • The spirolide displaced [ 125 I]α-bungarotoxin binding to Torpedo membranes (Ki = 0.028 nM) and in HEK-293 cells expressing chick chimeric α7-5HT 3 nAChR (Ki = 0.11 nM). (mdpi.com)
  • 2000). Correlative evidence for the involvement of brain nAChRs in cognitive dysfunction associated with neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, value of approximately 50 ␮M and shows comparable efficacy to ACh in oocyte experiments. (docme.ru)
  • Finally, pharmacological strategies focused on neuronal nAChRs are discussed as possible therapeutic avenues that may ameliorate the cognitive deficits of schizophrenia. (springer.com)
  • NACHO knockout mice show abnormalities in locomotor and cognitive behaviors compatible with nAChR deficiency and underscore the importance of this chaperone for physiology and disease associated with nAChRs. (viewpoint.fr)
  • In the postsynaptic cytoplasm, immunolabeling is associated with spine apparatus and other membranous structures, suggesting that 7 nAChRs may undergo dynamic regulation, with insertion into the synapse and subsequent internalization. (open.ac.uk)