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.
One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.
A 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.
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.
An object or a situation that can serve to reinforce a response, to satisfy a motive, or to afford pleasure.
Inhaling and exhaling the smoke of burning TOBACCO.
Tobacco used to the detriment of a person's health or social functioning. Tobacco dependence is included.
The N-glucuronide conjugate of cotinine is a major urinary metabolite of NICOTINE. It thus serves as a biomarker of exposure to tobacco SMOKING. It has CNS stimulating properties.
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.
A member of the NICOTINIC ACETYLCHOLINE RECEPTOR subfamily of the LIGAND-GATED ION CHANNEL family. It consists entirely of pentameric a7 subunits expressed in the CNS, autonomic nervous system, vascular system, lymphocytes and spleen.
Drugs that bind to nicotinic cholinergic receptors (RECEPTORS, NICOTINIC) and block the actions of acetylcholine or cholinergic agonists. Nicotinic antagonists block synaptic transmission at autonomic ganglia, the skeletal neuromuscular junction, and at central nervous system nicotinic synapses.
The study of natural phenomena by observation, measurement, and experimentation.
Educational institutions providing facilities for teaching and research and authorized to grant academic degrees.
Critical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws. (Webster, 3d ed)
All of the divisions of the natural sciences dealing with the various aspects of the phenomena of life and vital processes. The concept includes anatomy and physiology, biochemistry and biophysics, and the biology of animals, plants, and microorganisms. It should be differentiated from BIOLOGY, one of its subdivisions, concerned specifically with the origin and life processes of living organisms.
The application of scientific knowledge to practical purposes in any field. It includes methods, techniques, and instrumentation.
The biological science concerned with the life-supporting properties, functions, and processes of living organisms or their parts.
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.
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.
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.
A genus of the Torpedinidae family consisting of several species. Members of this family have powerful electric organs and are commonly called electric rays.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.

Neu differentiation factor stimulates phosphorylation and activation of the Sp1 transcription factor. (1/4103)

Neu differentiation factors (NDFs), or neuregulins, are epidermal growth factor-like growth factors which bind to two tyrosine kinase receptors, ErbB-3 and ErbB-4. The transcription of several genes is regulated by neuregulins, including genes encoding specific subunits of the acetylcholine receptor at the neuromuscular junction. Here, we have examined the promoter of the acetylcholine receptor epsilon subunit and delineated a minimal CA-rich sequence which mediates transcriptional activation by NDF (NDF-response element [NRE]). Using gel mobility shift analysis with an NRE oligonucleotide, we detected two complexes that are induced by treatment with neuregulin and other growth factors and identified Sp1, a constitutively expressed zinc finger phosphoprotein, as a component of one of these complexes. Phosphatase treatment, two-dimensional gel electrophoresis, and an in-gel kinase assay indicated that Sp1 is phosphorylated by a 60-kDa kinase in response to NDF-induced signals. Moreover, Sp1 seems to act downstream of all members of the ErbB family and thus may funnel the signaling of the ErbB network into the nucleus.  (+info)

(S)-(-)-Cotinine, the major brain metabolite of nicotine, stimulates nicotinic receptors to evoke [3H]dopamine release from rat striatal slices in a calcium-dependent manner. (2/4103)

Cotinine, a major peripheral metabolite of nicotine, has recently been shown to be the most abundant metabolite in rat brain after peripheral nicotine administration. However, little attention has been focused on the contribution of cotinine to the pharmacological effects of nicotine exposure in either animals or humans. The present study determined the concentration-response relationship for (S)-(-)-cotinine-evoked 3H overflow from superfused rat striatal slices preloaded with [3H]dopamine ([3H]DA) and whether this response was mediated by nicotinic receptor stimulation. (S)-(-)-Cotinine (1 microM to 3 mM) evoked 3H overflow from [3H]DA-preloaded rat striatal slices in a concentration-dependent manner with an EC50 value of 30 microM, indicating a lower potency than either (S)-(-)-nicotine or the active nicotine metabolite, (S)-(-)-nornicotine. As reported for (S)-(-)-nicotine and (S)-(-)-nornicotine, desensitization to the effect of (S)-(-)-cotinine was observed. The classic nicotinic receptor antagonists mecamylamine and dihydro-beta-erythroidine inhibited the response to (S)-(-)-cotinine (1-100 microM). Additionally, 3H overflow evoked by (S)-(-)-cotinine (10-1000 microM) was inhibited by superfusion with a low calcium buffer. Interestingly, over the same concentration range, (S)-(-)-cotinine did not inhibit [3H]DA uptake into striatal synaptosomes. These results demonstrate that (S)-(-)-cotinine, a constituent of tobacco products and the major metabolite of nicotine, stimulates nicotinic receptors to evoke the release of DA in a calcium-dependent manner from superfused rat striatal slices. Thus, (S)-(-)-cotinine likely contributes to the neuropharmacological effects of nicotine and tobacco use.  (+info)

Retrotransposons transcribed preferentially in proximal tubules of salt-hypertensive rats. (3/4103)

BACKGROUND: The kidney is considered to play an important etiologic role in salt-sensitive hypertension. The aim of the present study was to isolate genes whose expression differs between the kidneys of salt-hypertensive and control rats using an mRNA differential display method. METHODS: Dahl salt-sensitive (DS) and control salt-resistant rats (DR) were fed a 0.3% or 8% NaCl diet. Renal RNA was amplified by RNA arbitrarily primed polymerase chain reaction (RAP-PCR) and compared among DR 0.3%, DR 8%, DS 0.3%, and DS 8%. Gene expression and localization were examined by Northern blotting, RNase protection assay, and in situ hybridization. Full-length nucleotide sequence was determined by screening a DS rat kidney cDNA library. RESULTS: We identified one differentially displayed clone, and its expression was greater in DS than DR, which was not affected by salt loading. The sequence was 90% homologous to the 3'-noncoding region of the nicotinic acetylcholine receptor alpha7 subunit gene. Its expression was kidney-specific, and was localized in the proximal tubules. The transcript level was markedly increased precedent to the development of hypertension. Its expression was also high in other salt-sensitive rats, and low in normotensive Sprague-Dawley and Wistar rats. The full-length cDNA contained elements homologous to the retroviral pol gene, a primer binding site sequence for reverse transcriptase, and long-terminal repeats. CONCLUSION: These results demonstrated that the newly identified transcripts (REPT1) belong to a novel retrotransposon family, which showed unique strain-, age-, tissue-, and cell type-specific expression pattern.  (+info)

N-type voltage-dependent calcium channels mediate the nicotinic enhancement of GABA release in chick brain. (4/4103)

The role of voltage-dependent calcium channels (VDCCs) in the nicotinic acetylcholine receptor (nAChR)-mediated enhancement of spontaneous GABAergic inhibitory postsynaptic currents (IPSCs) was investigated in chick brain slices. Whole cell recordings of neurons in the lateral spiriform (SpL) and ventral lateral geniculate (LGNv) nuclei showed that cadmium chloride (CdCl2) blocked the carbachol-induced increase of spontaneous GABAergic IPSCs, indicating that VDCCs might be involved. To conclusively show a role for VDCCs, the presynaptic effect of carbachol on SpL and LGNv neurons was examined in the presence of selective blockers of VDCC subtypes. omega-Conotoxin GVIA, a selective antagonist of N-type channels, significantly reduced the nAChR-mediated enhancement of gamma-aminobutyric acid (GABA) release in the SpL by 78% compared with control responses. Nifedipine, an L-type channel blocker, and omega-Agatoxin-TK, a P/Q-type channel blocker, did not inhibit the enhancement of GABAergic IPSCs. In the LGNv, omega-Conotoxin GVIA also significantly reduced the nAChR-mediated enhancement of GABA release by 71% from control values. Although omega-Agatoxin-TK did not block the nicotinic enhancement, L-type channel blockers showed complex effects on the nAChR-mediated enhancement. These results indicate that the nAChR-mediated enhancement of spontaneous GABAergic IPSCs requires activation of N-type channels in both the SpL and LGNv.  (+info)

Light-induced calcium influx into retinal axons is regulated by presynaptic nicotinic acetylcholine receptor activity in vivo. (5/4103)

Visual activity is thought to be a critical factor in controlling the development of central retinal projections. Neuronal activity increases cytosolic calcium, which was hypothesized to regulate process outgrowth in neurons. We performed an in vivo imaging study in the retinotectal system of albino Xenopus laevis tadpoles with the fluorescent calcium indicator calcium green 1 dextran (CaGD) to test the role of calcium in regulating axon arbor development. We find that visual stimulus to the retina increased CaGD fluorescence intensity in retinal ganglion cell (RGC) axon arbors within the optic tectum and that branch additions to retinotectal axon arbors correlated with a local rise in calcium in the parent branch. We find three types of responses to visual stimulus, which roughly correlate with the ON, OFF, and SUSTAINED response types of RGC reported by physiological criteria. Imaging in bandscan mode indicated that patterns of calcium transients were nonuniform throughout the axons. We tested whether the increase in calcium in the retinotectal axons required synaptic activity in the retina; intraocular application of tetrodotoxin (10 microM) or nifedipine (1 and 10 microM) blocked the stimulus-induced increase in RGC axonal fluorescence. A second series of pharmacological investigations was designed to determine the mechanism of the calcium elevation in the axon terminals within the optic tectum. Injection of bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid-AM (BAPTA-AM) (20 mM) into the tectal ventricle reduced axonal calcium levels, supporting the idea that visual stimulation increases axonal calcium. Injection of BAPTA (20 mM) into the tectal ventricle to chelate extracellular calcium also attenuated the calcium response to visual stimulation, indicating that calcium enters the axon from the extracellular medium. Caffeine (10 mM) caused a large increase in axonal calcium, indicating that intracellular stores contribute to the calcium signal. Presynaptic nicotinic acetylcholine receptors (nAChRs) may play a role in axon arbor development and the formation of the topographic retinotectal projection. Injection of nicotine (10 microM) into the tectal ventricle significantly elevated RGC axonal calcium levels, whereas application of the nAChR antagonist alphaBTX (100 nM) reduced the stimulus-evoked rise in RGC calcium fluorescence. These data suggest that light stimulus to the retina increases calcium in the axon terminal arbors through a mechanism that includes influx through nAChRs and amplification by calcium-induced calcium release from intracellular calcium stores. Such a mechanism may contribute to developmental plasticity of the retinotectal system by influencing both axon arbor elaboration and the strength of synaptic transmission.  (+info)

NMR spatial structure of alpha-conotoxin ImI reveals a common scaffold in snail and snake toxins recognizing neuronal nicotinic acetylcholine receptors. (6/4103)

A 600 MHz NMR study of alpha-conotoxin ImI from Conus imperialis, targeting the alpha7 neuronal nicotinic acetylcholine receptor (nAChR), is presented. ImI backbone spatial structure is well defined basing on the NOEs, spin-spin coupling constants, and amide protons hydrogen-deuterium exchange data: rmsd of the backbone atom coordinates at the 2-12 region is 0.28 A in the 20 best structures. The structure is described as a type I beta-turn (positions 2-5) followed by a distorted helix (positions 5-11). Similar structural patterns can be found in all neuronal-specific alpha-conotoxins. Highly mobile side chains of the Asp-5, Arg-7 and Trp-10 residues form a single site for ImI binding to the alpha7 receptor. When depicted with opposite directions of the polypeptide chains, the ImI helix and the tip of the central loop of long chain snake neurotoxins demonstrate a common scaffold and similar positioning of the functional side chains, both of these structural elements appearing essential for binding to the neuronal nAChRs.  (+info)

Selective effects of a 4-oxystilbene derivative on wild and mutant neuronal chick alpha7 nicotinic receptor. (7/4103)

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)

Regulation of alpha4beta2 nicotinic receptor desensitization by calcium and protein kinase C. (8/4103)

Neuronal nicotinic acetylcholine receptor (nAChR) desensitization is hypothesized to be a trigger for long-term changes in receptor number and function observed after chronic administration of nicotine at levels similar to those found in persons who use tobacco. Factors that regulate desensitization could potentially influence the outcome of long-lasting exposure to nicotine. The roles of Ca2+ and protein kinase C (PKC) on desensitization of alpha4beta2 nAChRs expressed in Xenopus laevis oocytes were investigated. Nicotine-induced (300 nM; 30 min) desensitization of alpha4beta2 receptors in the presence of Ca2+ developed in a biphasic manner with fast and slow exponential time constants of tauf = 1.4 min (65% relative amplitude) and taus = 17 min, respectively. Recovery from desensitization was reasonably well described by a single exponential with taurec = 43 min. Recovery was largely eliminated after replacement of external Ca2+ with Ba2+ and slowed by calphostin C (taurec = 48 min), an inhibitor of PKC. Conversely, the rate of recovery was enhanced by phorbol-12-myristate-13-acetate (taurec = 14 min), a PKC activator, or by cyclosporin A (with taurec = 8 min), a phosphatase inhibitor. alpha4beta2 receptors containing a mutant alpha4 subunit that lacks a consensus PKC phosphorylation site exhibited little recovery from desensitization. Based on a two-desensitized-state cyclical model, it is proposed that after prolonged nicotine treatment, alpha4beta2 nAChRs accumulate in a "deep" desensitized state, from which recovery is very slow. We suggest that PKC-dependent phosphorylation of alpha4 subunits changes the rates governing the transitions from "deep" to "shallow" desensitized conformations and effectively increases the overall rate of recovery from desensitization. Long-lasting dephosphorylation may underlie the "permanent" inactivation of alpha4beta2 receptors observed after chronic nicotine treatment.  (+info)

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。
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…
Radiant insights, inc Neuronal Acetylcholine Receptor Subunit Alpha 7 (CHRNA7) - Pipeline Review, H2 2016, provides in depth analysis on Neuronal Acetylcholine Receptor Subunit Alpha 7 (CHRNA7) targeted pipeline therapeutics. The report provides comprehensive information on the Neuronal Acetylcholine Receptor Subunit Alpha 7 (CHRNA7) , targeted therapeutics, complete with analysis by indications, stage of development,…
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 ...
Thank you for sharing this Molecular Pharmacology article.. NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.. ...
Structure and backbone dynamics of a selectively [(15)N]Leu-labeled 28-residue segment of the extended second transmembrane domain (TM2e) of the human neuronal nicotinic acetylcholine receptor (nAChR) beta(2) subunit were studied by (1)H and (15)N solution-state NMR in dodecylphosphocholine micelles …
Fingerprint Dive into the research topics of Stable expression of the mouse nicotinic acetylcholine receptor in mouse fibroblasts: Comparison of receptors in native and transfected cells. Together they form a unique fingerprint. ...
TY - JOUR. T1 - Interaction of benzylidene-anabaseine analogues with agonist and allosteric sites on muscle nicotinic acetylcholine receptors. AU - Arias, H. R.. AU - Xing, H.. AU - MacDougall, K.. AU - Blanton, M. P.. AU - Soti, F.. AU - Kern, W. R.. PY - 2009/5/1. Y1 - 2009/5/1. N2 - Background and purpose: Benzylidene-anabaseines (BAs) are partial agonists of the α7 nicotinic acetylcholine receptor (nAChR) but their mechanism(s) of action are unknown. Our study explores several possibilities, including direct interactions of BAs with the nAChR channel. Experimental approach: Functional and radioligand-binding assays were used to examine the interaction of two BA analogues, 3-(2,4-dimethoxybenzylidene)-anabaseine (DMXBA) and Its primary metabolite 3-(4-hydroxy-2-methoxybenzylidene)anabaseine (4OH-DMXBA) with both agonist and non-competitive antagonist (NCA)-bindlng sites on muscle-type nAChRs. Key results: Both BAs non-competitively inhibited ACh activation of human fetal muscle nAChRs and ...
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。
Naturally occurring genetic variability in the nicotinic acetylcholine receptor alpha4 and alpha7 subunit genes and phenotypic diversity in humans and mice Journal Article ...
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.
TY - JOUR. T1 - Developmental mRNA expression of the α10 nicotinic acetylcholine receptor subunit in the rat cochlea. AU - Morley, Barbara J.. AU - Simmons, Dwayne D.. PY - 2002/11/15. Y1 - 2002/11/15. N2 - A recently discovered α10 subunit of the nicotinic acetylcholine receptor (nAChR) family is believed to form a heteromeric receptor with the α9 nAChR subunit in auditory hair cells. In the present study, the α10 nAChR subunit expression in the developing and adult rat inner ear was analyzed by PCR and localized using isotopic in situ hybridization. Unlike the α9 subunit, the α10 subunit was not detected at embryonic day 18 (E18). From E21 through postnatal day 15 (P15), the α10 subunit was localized over both inner hair cell (IHC) and outer hair cell (OHC) regions, but in the mature cochlea detectable levels of α10 mRNA were found only over the OHC region. From E21 through adult ages, there was also a small but consistent basal to apical gradient of α10 expression; that is, higher ...
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
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 ...
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
It is well established that nicotinic receptors in the mammalian striatum are involved in modulation of the release of several neurotransmitters, including dopamine. In addition, nicotinic receptors with high affinity for agonists have generally been found to be reduced in the striatum in Parkinsons disease. In the present study antibodies have been used to examine which subunits contribute to the striatal nicotinic receptor loss in Parkinsons disease, and whether the reduction in [(3)H]nicotine binding correlates with synaptic loss. Autopsy tissue from the putamen of 12 Parkinsons disease cases and 12 age-matched control subjects was analysed by immunoblotting using antibodies against recombinant peptides specific for alpha3, alpha4, alpha7, beta2 and beta4 nicotinic acetylcholine receptor (nAChR) subunits and the synaptic marker synaptophysin, in conjunction with assessment of [(3)H]nicotine binding by autoradiography. The data indicate that there is no loss of alpha3, alpha4, alpha7 and beta2
The cysteine-rich with EGF-like domains 2 (CRELD2) protein interacts with the large cytoplasmic domain of human neuronal nicotinic acetylcholine receptor alpha4 and beta2 subunits. Academic Article 2005 ...
TY - JOUR. T1 - Alpha 4-2 beta 2 and other nicotinic acetylcholine receptor subtypes as targets of psychoactive and addictive drugs. AU - Connolly, John. AU - Boulter, Jim. AU - Heinemann, Stephen F.. PY - 1992/3. Y1 - 1992/3. N2 - 1. Xenopus oocytes were injected with various muscle and neuronal nicotinic acetylcholine receptor (ACh receptor, cholinoceptor) subunit RNA combinations and their pharmacological properties studied using two-electrode voltage clamp. The functional expression of one of these combinations, rat alpha 4-2 beta 2, has not been previously described. The alpha 4-2 mRNA is a splicing variant transcribed from the alpha 4 gene. In the experiments reported here, the alpha 4-2 beta 2 subtype was functionally indistinguishable from the alpha 4-1 beta 2 subtype. 2. For each subtype, the relative potency of nicotine compared with acetylcholine was obtained by estimating the relative concentration of nicotine which would elicit the same current response as 0.1 microM Ach. The ratios ...
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 ...
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 ...
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
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 ...
Title: Neuronal Nicotinic Receptors as Brain Targets for Pharmacotherapy of Drug Addiction. VOLUME: 7 ISSUE: 5. Author(s):Shafiqur Rahman, Gretchen Y. Lopez-Hernandez, William A. Corrigall and Roger L. Papke. Affiliation:(SR) Department of Pharmaceutical Sciences, South Dakota State University, College of Pharmacy, Brookings, SD 57007, USA.. Keywords:Drug addiction, nicotinic receptors, nicotine, alcohol, cocaine, methamphetamine, opiate, dopamine. Abstract: Nicotine addiction and other forms of drug addiction continue to be significant public health problems in the United States and the rest of the world. Accumulated evidence indicates that brain nicotinic acetylcholine receptors (nAChRs) are a heterogenous family of ion channels expressed in the various parts of the brain. A growing body of preclinical studies suggests that brain nAChRs are critical targets for the development of pharmacotherapies for nicotine and other drug addictions. In this review, we will discuss the nAChR subtypes, their ...
Alpha6-containing nicotinic acetylcholine receptors are primarily within neurons from the midbrain dopaminergic (DA) system, recommending these receptors get excited about medicine pay back and dependence potentially. with bath program, however, not during intracellular administration, which inhibition isnt use-dependent. Additionally, in oocytes, cocaine both 6N/3C23-nAChRs and 6M211L/3IC23-nCAhRs inhibits likewise, recommending that cocaine may not respond over the 3 transmembrane domains of chimeric 6N/3C23-nAChR. In isolated VTA DA neurons mechanically, cocaine abolishes 6*-nAChR-mediated improvement of spontaneous inhibitory postsynaptic currents (sIPSCs). Collectively, these research supply the initial evidence that cocaine inhibits the function of both heterologously and naturally portrayed 6*-nAChRs directly. These findings claim that 6*-nAChRs might provide a book pharmacological focus on mediating the consequences of cocaine and could underlie a book system of cocaine incentive and ...
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 ...
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
Block of neurotransmitter receptors at the neuromuscular junction (NMJ) has been shown to trigger upregulation of the number of synaptic vesicles released (quantal content, QC), a response termed homeostatic synaptic plasticity. The mechanism underlying this plasticity is not known. Here, we used selective toxins to demonstrate that block of α1-containing nicotinic acetylcholine receptors (nAChRs) at the NMJ of male and female mice triggers the upregulation of QC. Reduction of current flow through nAChRs, induced by drugs with antagonist activity, demonstrated that reduction in synaptic current per se does not trigger upregulation of QC. These data led to the remarkable conclusion that disruption of synaptic transmission is not sensed to trigger upregulation of QC. During studies of the effect of partial block of nAChRs on QC, we observed a small but reproducible increase in the decay kinetics of miniature synaptic currents. The change in kinetics was correlated with the increase in QC and raises the
TY - JOUR. T1 - Luminal and non-luminal non-competitive inhibitor binding sites on the nicotinic acetylcholine receptor (Review). AU - Arias, Hugo R.. PY - 1996/1/1. Y1 - 1996/1/1. N2 - The nicotinic acetylcholine receptor presents two very well differentiated domains for ligand binding that account for different cholinergic properties. In the hydrophilic extracellular region of the a subunit exist the binding sites for agonists such as the neurotransmitter acetylcholine, which upon binding trigger the channel opening, and for competitive antagonists such as d-tubocurarine, which compete for the former inhibiting its pharmacological action. For non-competitive inhibitors, a population of low-affinity binding sites have been found at the lipid-protein interface of the nicotinic acetylcholine receptor. In addition, at the M2 transmembrane domain, several high-affinity binding sites have been found for non-competitive inhibitors such as chlorpromazine, triphenylmethylphosphonium, the local ...
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 ...
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 ...
This study compares the lipid composition, including individual phospholipid molecular species of solubilized nAChR detergent complexes (nAChR-DCs) with those of the bulk lipids from their source, Torpedo californica (Tc) electric tissue. This lipidomic analysis revealed seventy-seven (77) phospholipid species in the Tc tissue. Analysis of affinity-purified nAChR-DCs prepared with C-12 to C-16 phospholipid analog detergents alkylphosphocholine (FC) and lysofoscholine (LFC) demonstrated that nAChRDCs prepared with FC12, LFC14, and LFC16 contained ,60 phospholipids/nAChR, which was more than twice of those prepared with FC14, FC16, and LFC12. Significantly, all the nAChR-DCs lacked ethanolamine and anionic phospholipids, contained only four cholesterol molecules, and a limited number of phospholipid molecular species per nAChR. Upon incorporation into oocytes, FC12 produce significant functionality, whereas LFC14 and LFC16 nAChR-DCs displayed an increased functionality as compared to the crude Tc ...
Description: Gamma-Aminobutyric Acid Receptor Subunit Alpha 5 (GABA(A) Receptor Subunit Alpha 5 or GABRA5) - Gamma-aminobutyric acid A receptor, alpha 5 or
Our recent study (J Natl Cancer Inst, 102, 1322‐1335, 2010) demonstrated that the α9‐nicotinic receptor (α9‐nAChR) was detected at higher levels in advanced‐stage breast tumor tissues (tumor/normal ,8 fold, n=276) of Taiwanese patients. This research group will focus on α9‐nAChR‐mediated tumorigenesis mechanisms and will establish novel therapeutic strategies to overcome drug resistance in breast cancer. This 3‐year proposal is comprised of the following aims: Year‐1 study: To explore the molecular mechanisms of α9‐nAChR‐mediated carcinogenesis, clinical samples of advanced stage tumor patients will be collected (component project‐1, CP‐1). A molecular epidemiology study of selected family history will be established (CP‐2). The role of breast tumor stem cells in advanced‐stage breast cancer and the development of stem cell‐killing drugs will be explored (CP‐3). Validation of the antitumor effects of α9‐nAChR‐specific antagonists, lead compounds ...
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 ...
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 ...
Ethylbenzene and para-xylene (p-xylene), but not the chemically closely related organic solvents ortho-xylene (o-xylene) and meta-xylene (m-xylene), are known to cause ototoxicity and irreversible hearing loss, though the underlying mechanisms are still unknown. In this study, effects of ethylbenzene and of p-, o-, and m-xylene on human heteromeric α9α10 nicotinic ... read more acetylcholine receptors (nAChRs) expressed in Xenopus oocytes were investigated using the two-electrode voltage clamp technique. ACh dose-dependently evoked an α9α10 nAChR-mediated ion current with an EC50 of 137 μM. When ACh is applied at a low concentration (10 μM), the nAChR-mediated ion current is inhibited by a low concentration (10 μM) of ethylbenzene and p-xylene, but not by the same concentration of the non-ototoxic solvents. At a high solvent concentration (300 μM), all solvents cause inhibition of the ion currents evoked by 10 μM ACh. Ion currents evoked by a near maximum-effective concentration ACh (1 ...
Transcripts for 9 and 10 nicotinic acetylcholine receptor (nAChR) subunits are located in diverse cells. being triggered by acetylcholine and choline however, not by nicotine. A conotoxin analog, RgIA4, potently, and selectively clogged mouse 910 nAChRs with low nanomolar affinity indicating that RgIA4 could be efficiently used to review murine 910 nAChR function. Earlier reviews indicated that RgIA4 attenuates chemotherapy-induced chilly allodynia. Right here we demonstrate that RgIA4 analgesic results pursuing oxaliplatin treatment are suffered for 21 times after last RgIA4 administration indicating that RgIA4 might provide long lasting safety against nerve harm. RgIA4 does not have activity at GABAB receptors; a bioluminescence resonance energy transfer assay was utilized to show that two additional analgesic -conotoxins, Vc1.1 and AuIB, also usually do not activate 686770-61-6 supplier GABABRs expressed in HEK cells. Collectively these findings additional support the focusing on of 910 ...
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. ...
INTRODUCTION: The α4β2 nicotinic receptor is of central importance in tobacco dependence, while the homomeric α7 receptor may also play a role. In this candidate gene study, we examine the association between 8 single nucleotide polymorphisms (SNPs) in genes coding for nicotinic acetylcholine receptor subunits α4 (rs1044396, rs2273504, rs2236196, and rs2273502), α7 (rs2133965 and rs4779969), and β2 (rs2072660 and rs2072661) and smoking abstinence in a cohort of quitters enrolled in a clinical trial of behavioral support. METHODS: Data were obtained from the Patch in Practice study, involving 925 smokers in the United Kingdom. All participants were given an 8-week course of 15 mg of transdermal nicotine replacement therapy and blood was taken for genotyping. RESULTS: Logistic regression analyses assessed the association between each selected SNP and smoking abstinence at 4, 12, 26, and 52 weeks. There were no statistically significant associations with smoking cessation success or nicotine intake
TY - JOUR. T1 - Central nicotinic acetylcholine receptor involved in Ca 2+- calmodulin-endothelial nitric oxide synthase pathway modulated hypotensive effects. AU - Cheng, Pei Wen. AU - Lu, Pei Jung. AU - Chen, Siang Ru. AU - Ho, Wen Yu. AU - Cheng, Wen Han. AU - Hong, Ling Zong. AU - Yeh, Tung Chen. AU - Sun, Gwo Ching. AU - Wang, Ling Lin. AU - Hsiao, Michael. AU - Tseng, Ching Jiunn. PY - 2011/7/1. Y1 - 2011/7/1. N2 - BACKGROUND AND PURPOSE Recent evidence has suggested that nicotine decreases blood pressure (BP) and heart rate (HR) in the nucleus tractus solitarii (NTS), indicating that nicotinic acetylcholine receptors (nAChRs) play an important role in BP control in the NTS. However, the signalling mechanisms involved in nAChR-mediated depressor effects in the NTS are unclear. Hence, the aim of this study was to investigate these signalling mechanisms. EXPERIMENTAL APPROACH Depressor responses to nicotine microinjected into the NTS of Wistar-Kyoto rats were elicited in the absence and ...
Fingerprint Dive into the research topics of Receptor-mediated tobacco toxicity: Acceleration of sequential expression of α5 and α7 nicotinic receptor subunits in oral keratinocytes exposed to cigarette smoke. Together they form a unique fingerprint. ...
Global antibody supplier and research reagent supplier to the life science community. Find antibodies and reagents all backed by our Guarantee+.
Kullberg, R. W. and Zheng, Y. C. and Todt, W. et al. (1994) Structure and expression of the nicotinic acetylcholine receptor beta subunit of Xenopus laevis. Receptors & Channels, 2 (1). pp. 23-31. ISSN 1060-6823. https://resolver.caltech.edu/CaltechAUTHORS:20151231-001701500 ...
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 ...
TY - JOUR. T1 - The role of nicotinic acetylcholine receptors in Alzheimers disease. AU - Oddo, Salvatore. AU - LaFerla, Frank M.. PY - 2006/3/1. Y1 - 2006/3/1. N2 - The two hallmark lesions of Alzheimers disease (AD) are extracellular amyloid plaques, mainly formed by a small peptide called amyloid-β (Aβ), and neurofibrillary tangles, which are intracellular inclusions formed by aggregates of hyperphosphorylated tau protein. One of the major neurochemical features of AD is the marked reduction of nicotinic acetylcholine receptors in disease-relevant brain regions such as the cerebral cortex and hippocampus. This loss is further compounded by the loss of cholinergic cells, which contributes to the cognitive dysfunction. This observation has had a major impact on therapeutic treatments, as efforts to restore cholinergic function such as the administration of acetylcholinesterase inhibitors have been, until recently, the major treatment options available for AD. Understanding the relationship ...
TY - JOUR. T1 - 6-[18F]fluoro-A-85380, a new PET tracer for the nicotinic acetylcholine receptor. T2 - Studies in the human brain and in vivo demonstration of specific binding in white matter. AU - Ding, Yu Shin. AU - Fowler, Joanna S.. AU - Logan, Jean. AU - Wang, Gene Jack. AU - Telang, Frank. AU - Garza, Victor. AU - Biegon, Anat. AU - Pareto, Deborah. AU - Rooney, William. AU - Shea, Colleen. AU - Alexoff, David. AU - Volkow, Nora D.. AU - Vocci, Frank. PY - 2004/9/1. Y1 - 2004/9/1. KW - A-85380. KW - Nicotine. KW - Nicotinic acetylcholine receptors. KW - Positron emission tomography. KW - Tobacco dependence. KW - White matter. UR - http://www.scopus.com/inward/record.url?scp=3242749145&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=3242749145&partnerID=8YFLogxK. U2 - 10.1002/syn.20051. DO - 10.1002/syn.20051. M3 - Article. C2 - 15236351. AN - SCOPUS:3242749145. VL - 53. SP - 184. EP - 189. JO - Synapse. JF - Synapse. SN - 0887-4476. IS - 3. ER - ...
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
There are currently no human or mouse genes associated with this disease in the MGI database. Synonyms: ENFL2; nocturnal frontal lobe epilepsy 2
The nicotinic acetylcholine receptor (nAChR) of Torpedo electric rays has been extensively characterized over the last three decades. However, the molecular mechanisms by which detergents influence membrane protein stability and function remain poorly understood, and elucidation of the dynamic detergent-lipid-protein interactions of solubilized membrane proteins is a largely unexplored research field. This study examined nine detergents upon nAChR solubilization and purification, to assess receptor lipid composition using GC (Gas Chromatography)-FID (Flame Ionization) and/or GC-MSD (Mass Selective Detectors), stability and aggregation state using A-SEC (Analytical Size-Exclusion Chromatography) and EM (Electron Microscopy), and planar lipid bilayers to measure ion channel function. Detergent solubilization of nAChR-enriched membranes did not result in significant native lipid depletion or destabilization. Upon purification, native lipid depletion occurred in all detergents, with lipid-analog ...
TY - JOUR. T1 - Electrical activity-dependent regulation of the acetylcholine receptor δ- subunit gene, MyoD, and myogenin in primary myotubes. AU - Dutton, E. K.. AU - Simon, A. M.. AU - Burden, S. J.. N1 - Copyright: Copyright 2018 Elsevier B.V., All rights reserved.. PY - 1993. Y1 - 1993. N2 - Expression of the skeletal muscle acetylcholine receptor (AChR) is regulated by nerve-evoked muscle activity. Studies using transgenic mice have shown that this regulation is controlled largely by transcriptional mechanisms because responsiveness to electrical activity can be conferred by transgenes containing cis-acting sequences from the AChR subunit genes. The lack of a convenient muscle cell culture system for studying electrical activity-dependent gene regulation, however, has made it difficult to identify the important cis-acting sequences and to characterize an electrical activity-dependent signaling pathway. We developed a muscle culture system to study the mechanisms of electrical ...
Summary is not available for the mouse gene. This summary is for the human ortholog.] Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels formed by a pentameric arrangement of alpha and beta subunits to create distinct muscle and neuronal receptors. Neuronal receptors are found throughout the peripheral and central nervous system where they are involved in fast synaptic transmission. This gene encodes an alpha subunit that is widely expressed in the brain. The proposed structure for nAChR subunits is a conserved N-terminal extracellular domain followed by three conserved transmembrane domains, a variable cytoplasmic loop, a fourth conserved transmembrane domain, and a short C-terminal extracellular region. Mutations in this gene cause autosomal dominant nocturnal frontal lobe epilepsy type 4. Single nucleotide polymorphisms (SNPs) in this gene have been associated with nicotine dependence. [provided by RefSeq, Nov 2009 ...
Galantamine: Effect on nicotinic receptor binding, acetylcholinesterase inhibition, and learning Diana S. Woodruff-Pak, Richard W. Vogel III, and Gary L.
Old drugs, new tricks. Early promising anecdotal reports of treatment success using quinidine in drug-resistant epilepsy of infancy with migrating focal seizures caused by potassium channel gene KCNT1 gain-of-function mutations have been followed by mixed results from other investigators. And a small randomized trial of oral quinidine in patients with severe autosomal dominant nocturnal frontal lobe epilepsy due to KCNT1 mutations proved negative (Neurology. 2018 Jan 2;90(1):e67-e72. doi: 10.1212/WNL.0000000000004769. Epub 2017 Dec 1). An international group of investigators have asserted on the basis of an initial 15-patient series that the sodium-channel blockers carbamazepine and phenytoin should be considered first-line therapy in patients with KCNQ2 encephalopathy. They argued that early recognition and treatment of the disorder may be key to reducing the associated neurodevelopmental impairment (Epilepsia. 2015 May;56[5]:685-91). Time to reconceptualize epilepsy?. These potential new uses ...
BioAssay record AID 145519 submitted by ChEMBL: Nicotinic acetylcholine receptor binding activity was determined by ability to displace [3H]- (-) cytisine binding from whole rat brain synaptic membranes..
TY - JOUR. T1 - Block by apomorphine of acetylcholine receptor channels expressed in Xenopus oocytes. AU - Nakazawa, Ken. AU - Akiyama, Takami. AU - Inoue, Kazuhide. PY - 1994/11/15. Y1 - 1994/11/15. N2 - Effects of apomorphine and other compounds related to dopamine receptors on nicotinic acetylcholine receptor channels were investigated by expressing functional channels in Xenopus oocytes. When channels were expressed with a combination of α3 and β4 subunits, acetylcholine activated an inward current, and apomorphine suppressed the current in a concentration-dependent manner with an IC50 value of about 3 μM. SKF38393 (R(+)-1-phehyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol; dopamine D1 receptor agonist; 3 and 30 μM), quinpirole (dopamine D2 receptor agonist; 30 μM), SCH23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine; dopamine D1 receptor antagonist; 10 μM) or sulpiride (dopamine D2 receptor antagonist; 10 μM) also inhibited the ...
Nicotinic acetylcholine receptors (nAChRs) are expressed throughout the central nervous system, including on neuron populations that control breathing. The specific locations of nAChRs on respiratory related neurons are relatively unknown and their presence on phrenic motor neurons (PMNs) could indicate a point at which developmental nicotine exposure may impact breathing. We hypothesize that application of nicotine to the PMNs will elicit changes in amplitude and area of respiratory motor bursting recorded from cervical 3-5 ventral roots due to the presence of nAChRs on PMNs. A brainstem spinal cord split-bath preparation was used to separately perfuse brainstem and spinal cord chambers with artificial cerebrospinal fluid (aCSF), and nicotinic aCSF was added to the spinal cord chamber. Burst amplitude and area under the curve were measured at baseline and during application of three different nicotine concentrations (400nM, 4M, 40M). Our results show that while 400nM nicotinic aCSF did ...
Interactions of benzophenone (BP) with the Torpedo nicotinic acetylcholine receptor (nAChR) were characterized by electrophysiological analyses, radioligand binding assays, and photolabeling of nAChR-rich membranes with [3H]BP to identify the amino acids contributing to its binding sites. BP acted as a low potency noncompetitive antagonist, reversibly inhibiting the ACh responses of nAChRs expressed in Xenopus oocytes (IC50 = 600 卩 and the binding of the noncompetitive antagonist [3H]tetracaine to nAChR-rich membranes (IC50 = 150 卩. UV irradiation at 365 nm resulted in covalent incorporation of [3H]BP into the nAChR subunits (d , a ߠ, ?), with photoincorporation limited to the nAChR transmembrane domain. Comparison of nAChR photolabeling in the closed state (absence of agonist) and desensitized state (equilibrated with agonist) revealed selective desensitized state labeling in the d subunit of dPhe-232 in dM1 and dPro-286/dIle-288 near the beginning of dM3 that are within a pocket at the ...
This gene encodes a nicotinic acetylcholine receptor, which belongs to a superfamily of ligand-gated ion channels that play a role in fast signal transmission at synapses. These pentameric receptors can bind acetylcholine, which causes an extensive change in conformation that leads to the opening of an ion-conducting channel across the plasma membrane. This protein is an integral membrane receptor subunit that can interact with either nAChR beta-2 or nAChR beta-4 to form a functional receptor. Mutations in this gene cause nocturnal frontal lobe epilepsy type 1. Polymorphisms in this gene that provide protection against nicotine addiction have been described. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012 ...
The bad news, nicotine addiction has caused the deaths of millions from smoking-related diseases. The good news, nicotine can enhance cognitive performance. In an attempt to disentangle the brain networks that mediate nicotine reward and relevant cognitive functions, Maskos et al. have developed an injectable lentiviral vector that delivers functional nicotinic acetylcholine receptors to defined regions of the mouse brain. The technique was used to generate mice that express nicotinic receptors exclusively in the midbrain ventral tegmental area, the VTA, which contains dopamine reward neurons and is associated with the response to drugs of abuse. The experiment showed that these receptors in the VTA are sufficient for all behavioural and physiological phenomena associated with nicotine dependence. And they are also involved in the higher brain or cognitive functions in the mouse. Nicotines good and bad sides are, it seems, intimately entangled and originate from a phylogenetically ancient part of
Nicorette, Nicorette (mint) (nicotine polacrilex) is a small molecule pharmaceutical. Nicotine polacrilex was first approved as Nicorette on 1996-02-09. It is used to treat tobacco use disorder and ulcerative colitis in the USA. It is known to target neuronal acetylcholine receptor subunit alpha-4, neuronal acetylcholine receptor subunit alpha-9, neuronal acetylcholine receptor subunit alpha-10, potassium voltage-gated channel subfamily D member 3, neuronal acetylcholine receptor subunit alpha-3, and transient receptor potential cation channel subfamily A member 1. Nicotines patent is valid until 2028-04-30 (FDA).
TY - JOUR. T1 - Purification and characterization of a protein tyrosine phosphatase which dephosphorylates the nicotinic acetylcholine receptor. AU - Mei, Lin. AU - Huganir, Richard L.. PY - 1991/12/1. Y1 - 1991/12/1. N2 - The nicotinic acetylcholine receptor (nAChR) is phosphorylated to a high stoichiometry on tyrosine residues both in vitro and in vivo. Moreover, tyrosine phosphorylation has been shown to regulate the functional properties of the receptor. We report here the purification and characterization of a protein tyrosine phosphatase that dephosphorylates tyrosine-phosphorylated nAChR from Torpedo electroplax, a tissue highly enriched in the nAChR. The 32P-labeled tyrosine phosphorylated nAChR was used as a substrate to monitor the enzyme activity during purification. The protein tyrosine phosphatase activity was purified using three consecutive cation-exchange columns (phosphocellulose, S Sepharose Fast Flow, Bio-Rex 70), followed by two affinity matrices (p-aminobenzylphosphonic ...
The anti-inflammatory properties of TC-2559, an α4β2 nicotinic acetylcholine receptor (nAChR) agonist, on cultured murine macrophages was investigated. TC-2559 suppressed the upregulation of CC-chemokine ligand 3 (CCL3) and interleukin-1β (IL-1β) following lipopolysaccharide (LPS) treatment in J774A.1 cells. TC-2559 inhibited the phosphorylation of signal transducer and activator of transcription 3 (pSTAT3) but not nuclear factor-κB p65 after LPS. Blockade of pSTAT3 by AG490 inhibited the upregulation of CCL3 and IL-1β after LPS. In conclusion, TC-2559-driven α4β2 nAChR signaling suppressed the upregulation of CCL3 and IL-1β by inhibiting pSTAT3 in inflammatory macrophages, resulting in the suppression of neuropathic pain. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.. ...
Long-term cigarette smoking increases the risk of gastric cancer mortality. Nicotine and NNK, tobacco-specific mitogens, were reported to correlate with cancer progression on gastric cancer. Since metastasis is the major cause of cancer death, the influence of nicotine on the migration of gastric cancer cells remains to be determined. In addition, how to improve the therapeutic efficacy is the important issue for gastric cancer. Our preliminary results indicated that nicotine or NNK treatment can enhance the migratory ability on gastric cancer. The enhancement effect was mediated through nicotinic acetylcholine receptor (nAChR). Silence of alpha7-nAChR expression may inhibit the enhanced effect by nicotine or NNK treatment, indicating that nAChR may be the target for preventing gastric cancer migration. Further, we also found that down-regulation of nAChR increased the sensitivity to chemo-therapy. Those result suggested that nAChR may be the novel therapeutic target for gastric cancer therapy. ...
Neuronal nicotinic ACh receptors (nAChRs) are present in the rat medial habenula (MHB) and interpeduncular nucleus (IPN), two brain regions connected through the fasciculus retroflexus (FR). The goal of the present study was to compare the electrophysiological and pharmacological characteristics of nAChRs located at pre- and postsynaptic sites within the MHB-IPN system. nAChRs located on the soma of IPN neurons were studied using patch-clamp techniques and a preparation of acutely isolated neurons. Whole-cell currents evoked by Ach and nicotine showed an intense rectification at positive membrane potentials. nAChR channels were relatively nonselective for cations, had a unitary conductance of 35 pS, and were activated by several nicotinic agonists with the following rank order: cytisine greater than ACh greater than nicotine greater than dimethylphenylpiperazinium (DMPP). They were blocked by mecamylamine, hexamethonium, curare, and dihydro-beta-erythroidine (DHBE), but were insensitive to ...
There are two main research projects in my laboratory funded by grants from the Canadian Institutes of Health Research (CIHR) and the Natural Sciences and Engineering Research Council of Canada (NSERC). Both involve the structural characterization of integral membrane proteins using biophysical methods.. The first is titled Structure and function of the nicotinic acetylcholine receptor in its membrane environment. The nicotinic acetylcholine receptor (nAChR) is a neurotransmitter-gated ion channel found at synapses located in both the nervous system and at neuromuscular junctions. The nAChR (and other homologs) plays a central role in rapid communication in the brain. Factors that influence the efficacy of synaptic communication play an important role in higher brain functions, such as memory and learning, etc. Lipids are potent modulators of nAChR function. Increasing evidence suggests that lipids play an important role modulating nAChR function under both normal and pathological conditions. ...
A major site of initiation of inflammatory responses upon physical perturbation(s) and infection by invading organisms is the skin. Control of responses in this organ is, in part, modulated by the neuronal nicotinic acetylcholine receptor (nAChR) alpha7. To further investigate the role of alpha7 in skin inflammatory responses, a local inflammatory response was induced by topical application of croton oil to the ear skin of wild-type (alpha7WT) and alpha7 knock-out (alpha7KO) mice. Cells infiltrating the inflamed tissue were characterized by flow cytometry and RNA analysis. Six hours following croton oil application, analysis of infiltrating cells showed that the alpha7KO mice exhibited a significantly enhanced number of cells, and specifically, of Ly6G positive neutrophils. Macrophage and lymphocyte infiltration was equivalent in the alpha7KO and alpha7WT mice. RNA analysis showed that IL-1β and IL-6 were increased significantly in the infiltrating cells of the alpha7KO mouse, although TNF failed to
Nicotinic receptors play an important role in modulating the activity of parasympathetic cardiac vagal neurons in the medulla. Previous work has shown nicotine acts via at least three mechanisms to excite brain stem premotor cardiac vagal neurons. Nicotine evokes a direct increase in holding current and facilitates both the frequency and amplitude of glutamatergic neurotransmission to cardiac vagal neurons. This study tests whether these nicotinic receptor-mediated responses are endogenously active, whether α4β2 and α7 nicotinic receptors are involved, and whether prenatal exposure to nicotine alters the magnitude of these responses and the types of nicotinic receptors involved. Application of neostigmine (10 μM) significantly increased the holding current, amplitude, and frequency of miniature excitatory postsynaptic current (mEPSC) glutamatergic events in cardiac vagal neurons. In unexposed animals, the nicotine-evoked facilitation of mEPSC frequency, but not mEPSC amplitude or holding current,
Search for abbreviations and long forms in lifescience, results along with the related PubMed / MEDLINE information and co-occurring abbreviations.
Polymorphisms in the gene for the α5 nicotinic acetylcholine receptor (nAChR) subunit are associated with vulnerability to nicotine addiction. However, the underlying normal functions of α5-containing nAChRs in the brain are poorly understood. Striatal dopamine (DA) transmission is critical to the acquisition and maintenance of drug addiction and is modulated strongly by nicotine acting at heteromeric β2-containing (β2*) nAChRs. We explored whether α5 subunits, as well as α4, α6, and β3 subunits, participate in the powerful regulation of DA release probability by β2* nAChRs in nucleus accumbens (NAc) core and in dorsal striatum [caudatoputamen (CPu)]. We detected evoked dopamine release using fast-scan cyclic voltammetry at carbon-fiber microelectrodes in striatal slices from mice with deletions of α4, α5, α6, or β3 subunits. We show that the nAChR subtypes that dominantly regulate dopamine transmission depend critically upon α5 subunits in the dorsal CPu in α4α5(non-α6)β2-nAChRs but
TY - JOUR. T1 - Nicotinic acetylcholine receptor. T2 - evidence for a functionally distinct receptor on human lymphocytes.. AU - Richman, David P. AU - Arnason, B. G.. PY - 1979/9. Y1 - 1979/9. N2 - The presence of three distinct cholinergic receptors on human lymphocytes was suggested by the effects of carbamoylcholine on lymphocyte proliferation in vitro. The cells responded to both 0.1 nM and 1 microM carbamoylcholine by increased proliferation which was blocked by the muscarinic antagonist atropine. This effect occurred in both mitogen-stimulated cells (maximum effect at 24 hr) and nonstimulated cells (maximum effect at 72 hr). In contrast, 1--10 nM carbamoylcholine produced diminished in vitro proliferation, an effect which was blocked by the nicotinic antagonists alpha-bungarotoxin and d-tubocurarine.. AB - The presence of three distinct cholinergic receptors on human lymphocytes was suggested by the effects of carbamoylcholine on lymphocyte proliferation in vitro. The cells responded to ...
The extracellular patch-clamp technique was used to examine how halothane, a general anesthetic, affects the properties of single nicotinic acetylcholine receptor channels of embryonic Xenopus skeletal muscle cells grown in culture. Under control conditions, single-channel events showed a bimodal distribution on the basis of current amplitudes. This distribution was maintained during exposure to halothane and its washout. In addition, the mean current value of the low-and high-amplitude channels was unaffected by the presence of the anesthetic at clinically relevant concentrations. In contrast, halothane shortened the burst durations of both channel types in a concentration-dependent manner. This shortening of burst durations may be an expression of the more rapid relaxation of the channel protein to the nonconducting state, possibly due to the disordering effect of the anesthetic on membrane lipids in which the receptor protein is embedded. This functional change, in the behavior of the ...
A nicotinic agonist is a drug that mimics the action of acetylcholine (ACh) at nicotinic acetylcholine receptors (nAChRs). The nAChR is named for its affinity for nicotine. Examples include nicotine (by definition), acetylcholine (the endogenous agonist of nAChRs), choline, epibatidine, lobeline, varenicline and cytisine. Nicotine has been known for centuries for its intoxicating effect. It was first isolated in 1828 from the tobacco plant by German chemists, Posselt and Reimann. The discovery of positive effects from nicotine on animal memory was discovered by in vivo researches in the mid 1980s. Those researches led to a new era in studies of nicotinic acetylcholine receptor (nAChR) and their stimulation but until then the focus had mainly been on nicotine addiction. The development of nAChR agonists began in the early 1990s after the discovery of nicotines positive effects. Some research showed a possible therapy option in preclinical researches. ABT-418 was one of the first in a series of ...
The nicotine metabolite ratio (NMR), a stable marker of nicotine clearance rate, is a robust predictor of smoking relapse. Individuals who are fast nicotine metabolizers have higher rates of relapse, compared to slow metabolizers, on nicotine replacement or placebo treatment. Nicotine exerts its reinforcing properties, in part, by binding to α4β2* nicotinic acetylcholine receptors (nAChRs) in the brain. The α4β2* nAChRs are abundant and have high affinity for nicotine relative to other nAChR subtypes. The goal of this project is to identify abstinence-induced changes in neuronal nicotinic receptor availability that may underlie risk for smoking relapse.. The investigators propose to utilize positron emission tomography (PET) imaging to examine the association of variation in nicotine metabolism with return to availability of α4β2* nAChRs during early abstinence. The investigators will measure α4β2* receptor availability using the PET radio-ligand 2-[18F]FA, administered with bolus ...
We investigated the role of the principal face of the β2 subunit in dFBr modulation of ACh currents on the α4β2-nAChR HS and LS isoforms. Our data indicate that mutation of residues in loops A and B alters both the magnitude of dFBr potentiation and pEC50 values. The β2 residues W176 (B loop) and Y120 (A loop) were found to significantly alter dFBr apparent potency and eliminate dFBr potentiation, suggesting that these residues may be a part of the dFBr-binding site. These data provide clues to the mechanism of dFBr potentiation. Several mutations [β2(W176A), β2(D179A), β2(T177A), β2(D217A), β2(Y120A), and β2(Y127A)] also altered ACh Imax and potency, even though they are not located in the ACh-binding cleft. Our findings provide evidence that suggests structural perturbations occurring within noncanonical binding interfaces alter the functional response to ACh on both α4β2-nAChR isoforms.. Previous mutations, specifically α1(S205) and α1(S206) [equivalent to nAChR β2(D217) and ...
Background & Purpose: Stroke is an important risk factor and one of the most devastating complications for bone fracture. We showed previously that bone fracture at the acute stage of ischemic stroke worsens, and activation of α7 nicotinic acetylcholine receptor (α7 nAchR) improves stroke recovery through attenuation of inflammation. We hypothesized that activation of α7 nAchR also improves blood-brain barrier integrity.. Methods: Permanent distal middle cerebral artery occlusion (pMCAO) was performed on C57BL/6J mice followed by tibia fracture 1 day later. Mice were treated intra-peritoneally with 0.8 mg/kg PHA 568487 (PHA, α7 nAchR-specific agonist), 6 mg/kg methyllycaconitine (MLA, α7 nAchR antagonist), or saline 1 and 2 days after pMCAO. Brain water content was assessed by measuring the wet and dry weight 3 days after pMCAO. The expression of monoamine oxidase B (MAO-B) in astrocytes and tight junction proteins was quantified in the peri-infarct region using immunostained brain sections ...
Like many other biologically active substances, acetylcholine exerts its effects by binding to and activating receptors located on the surface of cells. There are two main classes of acetylcholine receptor, nicotinic and muscarinic. They are named for chemicals that can selectively activate each type of receptor without activating the other: muscarine is a compound found in the mushroom Amanita muscaria; nicotine is found in tobacco.. Nicotinic acetylcholine receptors are ligand-gated ion channels permeable to sodium, potassium, and calcium ions. In other words, they are ion channels embedded in cell membranes, capable of switching from a closed to open state when acetylcholine binds to them; in the open state they allow ions to pass through. Nicotinic receptors come in two main types, known as muscle-type and neuronal-type. The muscle-type can be selectively blocked by curare, the neuronal-type by hexamethonium. The main location of muscle-type receptors is on muscle cells, as described in more ...
Phenthonium (Phen), a quaternary analog of hyoscyamine, is a blocker of muscarinic activity and an allosteric blocker of alpha(1)2 beta gamma epsilon nicotinic receptors. Specifically, Phenthonium increases the spontaneous release of acetylcholine at the motor endplate without depolarizing the muscle or inhibiting cholinesterase activity. This paper compares Phenthoniums effects on sympathetic transmission and on ganglionic nicotinic receptor activation. Neurotransmitter release and twitch of the rat vas deferens were induced either by electrical stimulation or by 1,1-dimethyl-4-phenylpiperazine (DMPP) activation of nicotinic receptors. Contractions independent of transmitter release were induced by noradrenaline and adenosine 5-triphosphate (ATP). Phenthonium inhibited transmitter release and depressed twitch without changing the responsiveness to noradrenaline or ATP. Twitch depression did not occur after K(+)-channel blockade with 4-aminopyridine (4-AP) or charybdotoxin. DMPP had a similar ...
Neuronal nicotinic AChRs (nAChRs) are implicated in the pathogenesis of diverse neurological disorders and in the regulation of small-cell lung carcinoma growth. Twelve subunits have been identified in vertebrates, and mutations of one are recognized in a rare form of human epilepsy. Mice with genetically manipulated neuronal nAChR subunits exhibit behavioral or autonomic phenotypes. Here, we report the first model of an acquired neuronal nAChR disorder and evidence for its pertinence to paraneoplastic neurological autoimmunity. Rabbits immunized once with recombinant α3 subunit (residues 1-205) develop profound gastrointestinal hypomotility, dilated pupils with impaired light response, and grossly distended bladders. As in patients with idiopathic and paraneoplastic autoimmune autonomic neuropathy, the severity parallels serum levels of ganglionic nAChR autoantibody. Failure of neurotransmission through abdominal sympathetic ganglia, with retention of neuronal viability, confirms that the ...
Introduction: alpha 7 nicotinic acetylcholine receptors (nAChRs) play an important role in vagus nerve-based cholinergic anti-inflammatory effects. This study was designed to assess the role of alpha 7 nAChRs in dextran sodium sulfate (DSS)-induced colitis in male and female mouse. We first compared disease activity and pathogenesis of colitis in alpha 7 knockout and wild-type mice. We then evaluated the effect of several alpha 7 direct and indirect agonists on the severity of disease in the DSS-induced colitis.
PubMed journal article: Presynaptic alpha 7- and beta 2-containing nicotinic acetylcholine receptors modulate excitatory amino acid release from rat prefrontal cortex nerve terminals via distinct cellular mechanisms. Download Prime PubMed App to iPhone, iPad, or Android
My laboratory is interested in the structural underpinnings of neurotransmitter-gated ion channel function. We are currently investigating the family of pentameric ligand-gated channels that includes the nicotinic acetylcholine receptors, 5-HT3, GABAA and glycine receptors as well as several receptors found in invertebrates. All of these receptors share a conserved 3D architecture, but there is limited atomic-resolution structural information for those found in eukaryotes. There are a number of poorly understood but fundamental receptor mechanisms that we aim to resolve through structure determination and careful biophysical analysis. We are fascinated by how binding of a small chemical transmitter to an extracellular domain of the receptor achieves opening of a gate in the membrane ,50 Å away, on a sub-millisecond timescale. We are also interested to understand the structural basis of the diverse selectivities for ions (charge and valence), mechanism(s) of desensitization and principles of ...
Nicotinic acetylcholine receptors (nAChRs) in the brain exhibit diverse functional properties and ubiquitous distribution. Yet, except for providing a
Lippiello, P., Beaver, J., Gatto, G., James, J., Jordan, K., Traina, V., & et al, . U. (2008). TC-5214 (S-(+)-mecamylamine): A neuronal nicotinic receptor modulator with antidepressant activity. CNS Neuroscience & Therapeutics, 14(4), 266 - 277 ...
Motor neurons become hyperexcitable during progression of amyotrophic lateral sclerosis (ALS). This abnormal firing behavior has been explained by changes in their membrane properties, but more recently it has been suggested that changes in premotor circuits may also contribute to this abnormal activity. The specific circuits that may be altered during development of ALS have not been investigated. Here we examined the Renshaw cell recurrent circuit that exerts inhibitory feedback control on motor neuron firing. Using two markers for Renshaw cells (calbindin and cholinergic nicotinic receptor subunit alpha2 [Chrna2]), two general markers for motor neurons (NeuN and vesicular acethylcholine transporter [VAChT]), and two markers for fast motor neurons (Chondrolectin and calcitonin-related polypeptide alpha [Calca]), we analyzed the survival and connectivity of these cells during disease progression in the Sod1G93A mouse model. Most calbindin-immunoreactive (IR) Renshaw cells survive to end stage but
Midbrain slices and electrophysiology. Midbrain slices containing the VTA and SNc were prepared from 15- to 24-d-old Sprague Dawley rats, wild-type C57BL/6J mice, or mutant mice that were anesthetized before decapitation (Xu et al., 1999;Orr-Urtreger et al., 2000). Slices (300-350 μm thick, rats; 200-250 μm, mice) were prepared following previously published procedures (Pidoplichko et al., 1997; Zhou et al., 2001). The cutting solution was either of the following and usually a 50/50% mixture of the two solutions (in mm): 230 sucrose, 1 KCl, 1.25 NaH2PO4, 30 NaHCO3, 1 CaCl2, 7 MgCl2, 25 d-glucose; and 144 NMDG, 1.5 KCl, 1.25 NaH2PO4, 30 NaHCO3, 2 CaCl2, 2 MgCl2, 25 d-glucose, 30 NaHCO3. The slices were then transferred to a holding chamber containing the bath solution (in mm): 125 NaCl, 2.5 KCl, 1.25 NaH2PO4, 21 NaHCO3, 2.5 CaCl2, 1 MgCl2, 25 d-glucose. The experimental chamber (0.5 ml capacity) had a continuously flowing bath solution (∼5 ml/min) at 32-34°C. The external solutions contained ...
Cohen, Bruce N. and Labarca, Cesar and Davidson, Norman et al. (1992) Mutations in M2 alter the selectivity of the mouse nicotinic acetylcholine receptor for organic and alkali metal cations. Journal of General Physiology, 100 (3). pp. 373-400. ISSN 0022-1295. PMCID PMC2229089. https://resolver.caltech.edu/CaltechAUTHORS:COHjgp92a ...
Granulocyte Macrophage Colony Stimulating Factor Receptor Subunit Alpha - Pipeline Review, H2 2017; Granulocyte Macrophage Colony Stimulating Factor Recep
RATIONALE: Diagnostic procedures, such as positron emission tomography (PET) using [18F]-labeled substance P antagonist receptor quantifier, may be effe
Supplementary MaterialsSupplementary Statistics. and TUG891 save the manifestation of type II collagen and aggrecan by preventing the reduction of SOX9 manifestation. Additionally, we demonstrate that the effects of GW9508 Fursultiamine on SOX9 manifestation are mediated through CREB and that GPR120 is indeed required for this effect. Therefore, agonism of GPR120 by GW9508 might be a potential restorative strategy to halt or prevent cartilage degradation. to simulate OA conditions [9]. SOX9 is definitely a central transcription element that plays an important part in chondrogenesis by mediating the transcription of type II collagen and aggrecan. SOX9 is definitely expressed during the developmental stage as well as with adults [10, 11]. Therefore, overexpression of SOX9 may have restorative potential. The cAMP-response element-binding protein (CREB) mediates SOX9 manifestation by binding to specific sites within the SOX9 proximal promoter region, and mutations at these sites have been shown to ...
Endotoxemia induces the release of TNF-α from macrophages, as part of an inflammatory process. Acetylcholine and nicotine inhibit the release of TNF-α from macrophages in vitro, through activation of nicotinic receptors. In animals, vagal nerve stimulation inhibits the increase in plasma TNF-α induced by endotoxemia in vivo (for review, see Tracey KJ. Nature 2002;420:853). It is proposed that acetylcholine diffuses from parasympathetic nerve terminals in reticuloendothelial organs, to inhibit inflammatory cells. Wang et al. studied the receptor subtype that mediates these actions. Nicotinic acetylcholine receptors are a family of ligand-gated pentameric ion channels. In humans, 16 different subunits have been identified (α1-7, α9-10, β1-4, δ, ε, and γ), and pentameric receptors are formed by various combinations of these subunits. It is known that the acetylcholine-sensitive TNF-α response is blocked by α-bungarotoxin, a peptide antagonist that binds to α1, α7, and α9. Biding of ...
Lung cancer is the most common cause of cancer death worldwide, with over one million cases annually1. To identify genetic factors that modify disease risk, we conducted a genome-wide association study by analysing 317,139 single-nucleotide polymorphisms in 1,989 lung cancer cases and 2,625 controls from six central European countries. We identified a locus in chromosome region 15q25 that was strongly associated with lung cancer (P = 9 times 10-10). This locus was replicated in five separate lung cancer studies comprising an additional 2,513 lung cancer cases and 4,752 controls (P = 5 times 10-20 overall), and it was found to account for 14% (attributable risk) of lung cancer cases. Statistically similar risks were observed irrespective of smoking status or propensity to smoke tobacco. The association region contains several genes, including three that encode nicotinic acetylcholine receptor subunits (CHRNA5, CHRNA3 and CHRNB4). Such subunits are expressed in neurons and other tissues, in ...
The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (also known as AMPA receptor, AMPAR, or quisqualate receptor ... "NMDA receptor activation dephosphorylates AMPA receptor glutamate receptor 1 subunits at threonine 840". J. Neurosci. 27 (48): ... AMPA receptor trafficking to the PSD in response to LTP[edit]. Once AMPA receptors are transported to the perisynaptic region ... AMPA receptors (AMPAR) are both glutamate receptors and cation channels that are integral to plasticity and synaptic ...
On the Discovery of the Nicotinic Acetylcholine Receptor Channel. Pp. 1-16 in R. A. J. Lester, ed. Nicotinic Receptors. ... For example, the characterization of the nicotinic acetylcholine receptor, the first neurotransmitter receptor to be identified ... Similarly, the muscarinic acetylcholine receptor takes its name from the fungal toxin muscarine. In 1959, Adolf Butenandt ...
DHNK is inactive at the α3β4-nicotinic acetylcholine receptor (IC50 > 100 μM) and is only very weakly active at the NMDA ... Robin A.J. Lester (11 November 2014). Nicotinic Receptors. Springer. pp. 445-. ISBN 978-1-4939-1167-7. Paul, Rajib K.; Singh, ... DHNK has been found to act as a potent and selective negative allosteric modulator of the α7-nicotinic acetylcholine receptor ( ... ketamine metabolites inhibit acetylcholine-evoked currents in α7 nicotinic acetylcholine receptors". European Journal of ...
Relative to ketamine, norketamine is much more potent as an antagonist of the α7-nicotinic acetylcholine receptor, and produces ... Robin A.J. Lester (11 November 2014). Nicotinic Receptors. Springer. pp. 445-. ISBN 978-1-4939-1167-7. v t e. ... but retain activity as potent antagonists of the α7-nicotinic acetylcholine receptor. A. P. Adams; J. N. Cashman; R. M. Grounds ... ketamine metabolites inhibit acetylcholine-evoked currents in α7 nicotinic acetylcholine receptors". European Journal of ...
"Nicotinic acetylcholine receptors: Introduction". IUPHAR Database. International Union of Basic and Clinical Pharmacology. ... The alkaloid nicotine from tobacco binds directly to the body's Nicotinic acetylcholine receptors, accounting for its ... "Molecular aspects of phytoestrogen selective binding at estrogen receptors". Journal of Pharmaceutical Sciences. 96 (8): 1879- ...
See also: Receptor/signaling modulators • Muscarinic acetylcholine receptor modulators • Nicotinic acetylcholine receptor ... Binding to the nicotinic receptor Shorter molecules like acetylcholine need two molecules to activate the receptor, one at each ... Fig.3 A simple illustration of how vecuronium binds to the nicotinic receptor. Its D-ring binds to the receptor at two points ... Each ACh-receptor has two receptive sites and activation of the receptor requires binding to both of them. Each receptor site ...
It may be hydrolysed by acetylcholine esterase (AchE) or bind to the nicotinic receptors located on the motor end plate. The ... Nondepolarizing agents, such as tubocurarine, block the agonist, acetylcholine, from binding to nicotinic receptors and ... Alternatively, depolarizing agents, such as succinylcholine, are nicotinic receptor agonists which mimic Ach, block muscle ... molecules results in a conformational change in the receptor that opens the sodium-potassium channel of the nicotinic receptor ...
The absorbed nicotine mimics nicotinic acetylcholine which when bound to nicotinic acetylcholine receptors prevents the ... These nicotinic acetylcholine receptors are located in the central nervous system and at the nerve-muscle junction of skeletal ... Wonnacott, S. (1997). "Presynaptic nicotinic ACh receptors". Trends in Neurosciences. 20 (2): 92-8. doi:10.1016/S0166-2236(96) ... However, since dopamine-releasing neurons are abundant on nicotine receptors, dopamine is released; and, in the nucleus ...
Nicotinic acetylcholine receptor 5. Mitochondrion A juvenile thymus shrinks with age. The nicotinic acetylcholine receptor For ... The antibodies in MG attack a normal human protein, the nicotinic acetylcholine receptor, or a related protein called MuSK, a ... If the diagnosis is suspected, serology can be performed: One test is for antibodies against the acetylcholine receptor; the ... gravis is an autoimmune disease which results from antibodies that block or destroy nicotinic acetylcholine receptors (AChR) at ...
It mimics the action of the neurotransmitter acetylcholine at nicotinic acetylcholine receptors in the brain and the ... Wonnacott S (February 1997). "Presynaptic nicotinic ACh receptors". Trends in Neurosciences. 20 (2): 92-8. doi:10.1016/S0166- ... The neuronal forms of the receptor are present both post-synaptically (involved in classical neurotransmission) and pre- ... but the term is usually reserved for the classical antihistamines that act upon the H1 histamine receptor. Antihistamines are ...
"Nicotinic acetylcholine receptors: Introduction". IUPHAR Database. International Union of Basic and Clinical Pharmacology. ... The alkaloid nicotine from tobacco binds directly to the body's Nicotinic acetylcholine receptors, accounting for its ...
... acts as a receptor agonist at most nicotinic acetylcholine receptors (nAChRs), except at two nicotinic receptor ... Nicotine acts as a receptor agonist at most nicotinic acetylcholine receptors (nAChRs), except at two nicotinic receptor ... Nicotine activates nicotinic receptors (particularly α4β2 nicotinic receptors) on neurons that innervate the ventral tegmental ... and α10 subunits of nicotinic acetylcholine receptors. Evidence suggests that nicotinic receptors which contain these subunits ...
De Biasi, M. (2009). "Nicotinic Receptors: Autonomic Neurons". Encyclopedia of Neuroscience. Elsevier. pp. 1135-1139. doi: ...
It is a nicotinic agonist, meaning it binds to nicotinic receptors in the body and mimics the effects of the neurotransmitter ... 336-337). Phantasmidine is a nicotinic agonist that acts at acetylcholine receptors. It mimics the effects of acetylcholine on ... 24 October 2013). "Nicotinic Acetylcholine Receptor Agonists". United States Patent Application Publication. 1 (12/583, 420): 1 ... Phantasmidine is selective for nicotinic acetylcholine receptors (nAChR) containing ß4 subunits; however, responses in ...
... and Nicotinic Receptors. Schizophrenia Bulletin, 24(2):189-202. ... Information from sensory receptors make their way to the brain ...
They have nicotinic acetylcholine receptors. Despite the shared origin of skeletal muscle cells and electrocytes in myogenic ... More recently, Torpedo californica electrocytes were used in the first sequencing of the acetylcholine receptor by Noda and ...
... is a high affinity, selective nicotinic α4β2* receptor partial agonist used in medical research for nicotinic ... April 2006). "Nicotinic alpha4beta2 receptor imaging agents: part II. Synthesis and biological evaluation of 2-[18F]fluoro-3-[2 ... January 2013). "Nicotinic α4β2 receptor imaging agents. Part IV. Synthesis and biological evaluation of 3-(2-(S)-3,4- ... May 2012). "Nicotinic acetylcholine receptors in rat forebrain that bind ¹⁸F-nifene: relating PET imaging, autoradiography, and ...
As above plus nicotinic acetylcholine receptor antagonist.. PO.. Protein binding = 80%; half-life = 2.6 days.. Opioid ... Partial agonist at the mu opioid receptor; agonist at delta opioid receptor; antagonist at kappa opioid receptor.. Sublingual, ... Full agonist at kappa opioid receptors, partial agonist/antagonist at the mu opioid receptors.[39]. IM, IV, SC.. Protein ... Kappa opioid receptor agonist; mu opioid receptor antagonist/partial agonist.. IM, IV, SC.. Bioavailability = 60-70%; protein ...
2000). "The nicotinic receptor beta 2 subunit is mutant in nocturnal frontal lobe epilepsy". Nat. Genet. 26 (3): 275-6. doi: ... Bracci L, Lozzi L, Rustici M, Neri P (1992). "Binding of HIV-1 gp120 to the nicotinic receptor". FEBS Lett. 311 (2): 115-8. doi ... 2002). "Changes in nicotinic acetylcholine receptor subunits expression in brain of patients with Down syndrome and Alzheimer's ... Anand R, Lindstrom J (1990). "Nucleotide sequence of the human nicotinic acetylcholine receptor beta 2 subunit gene". Nucleic ...
Ligand-gated ion channels such as the nicotinic acetylcholine receptor and GABAA receptor are composed of five subunits ... Sometimes the channel can be made from only one type of subunit, such as the α7 nicotinic receptor, which is made up from five ... "Receptor-receptor interactions within receptor mosaics. Impact on neuropsychopharmacology". Brain Research Reviews. 58 (2): 415 ... Graham AJ, Martin-Ruiz CM, Teaktong T, Ray MA, Court JA (August 2002). "Human brain nicotinic receptors, their distribution and ...
Dutertre, Sébastien; Lewis, Richard J. (2006). "Toxin insights into nicotinic acetylcholine receptors". Biochemical ... Myotoxins, which damage muscles by binding to a receptor, are small, basic peptides found in snake (such as rattlesnake) and ...
... has been shown to interact with Cholinergic receptor, nicotinic, alpha 1. Nicotinic acetylcholine receptor GRCh38: ... Beeson D, Jeremiah S, West LF, Povey S, Newsom-Davis J (1990). "Assignment of the human nicotinic acetylcholine receptor genes ... Wang ZZ, Hardy SF, Hall ZW (November 1996). "Assembly of the nicotinic acetylcholine receptor. The first transmembrane domains ... Wang ZZ, Hardy SF, Hall ZW (1996). "Assembly of the nicotinic acetylcholine receptor. The first transmembrane domains of ...
Cholinergic receptor, nicotinic, alpha 1 has been shown to interact with CHRND. Nicotinic acetylcholine receptor GRCh38: ... Bracci L, Lozzi L, Rustici M, Neri P (October 1992). "Binding of HIV-1 gp120 to the nicotinic receptor". FEBS Letters. 311 (2 ... Beeson D, Jeremiah S, West LF, Povey S, Newsom-Davis J (July 1990). "Assignment of the human nicotinic acetylcholine receptor ... Beeson D, Morris A, Vincent A, Newsom-Davis J (July 1990). "The human muscle nicotinic acetylcholine receptor alpha-subunit ...
Hyperstimulation of nicotinic and muscarinic receptors. When used in the central nervous system to alleviate neurological ... This results in continuous activation of acetylcholine receptors, which leads to the acute symptoms of TEPP poisoning. The ... June 2017). "Novel bipharmacophoric inhibitors of the cholinesterases with affinity to the muscarinic receptors M1 and M2". ... also an adenosine receptor antagonist) Rosmarinic acid - ester of caffeic acid. Found in plants species of family Lamiaceae. ...
March 2003). "Molecular identification of high and low affinity receptors for nicotinic acid". The Journal of Biological ... March 2003). "Molecular identification of nicotinic acid receptor". Biochemical and Biophysical Research Communications. 303 (1 ... Niacin (Nicotinic Acid, Nicotinamide)". Vitamins, 11. Niacin (Nicotinic Acid, Nicotinamide. Ullmann's Encyclopedia of ... including hydroxycarboxylic acid receptor 2 (HCA2)and hydroxycarboxylic acid receptor 3 (HCA3), which are highly expressed in ...
The nerve tissues which communicate with muscles contain a receptor called the nicotinic acetylcholine receptor. Stimulation of ... Curare notably functions to inhibit nicotinic acetylcholine receptors at the neuromuscular junction. Normally, these receptor ... Tsetlin, V.I; Hucho, F. (2004). "Snake and Snail Toxins Acting on Nicotinic Acetylcholine Receptors: Fundamental Aspects and ... Bungarotoxin is a compound with known interaction with nicotinic acetylcholine receptors (nAChRs), which constitute a family of ...
Antinicotinic agents operate on the nicotinic acetylcholine receptors. The majority of these are non-depolarising skeletal ... Nicotine also counteracts anticholinergics by activating nicotinic acetylcholine receptors. Caffeine (although an adenosine ... "Effect of Dextrometorphan and Dextrorphan on Nicotine and Neuronal Nicotinic Receptors: In Vitro and in Vivo Selectivity". ... "Effects of dextrorotatory morphinans on α3β4 nicotinic acetylcholine receptors expressed in Xenopus oocytes". European Journal ...
"Neuronal nicotinic receptors: a perspective on two decades of drug discovery research". Biochemical Pharmacology. Nicotinic ... It acts as a partial agonist at neuronal nicotinic acetylcholine receptors, binding to both the α3β4 and the α4β2 subtypes. ... Umana IC, Daniele CA, McGehee DS (Oct 2013). "Neuronal nicotinic receptors as analgesic targets: it's a winding road". Biochem ... Meyer, Michael D. (1 April 2006). "Neuronal nicotinic acetylcholine receptors as a target for the treatment of neuropathic pain ...
ISBN 978-3-540-22569-0. Soudijn W, van Wijngaarden I, Ijzerman AP (May 2007). "Nicotinic acid receptor subtypes and their ... HDL is removed by HDL receptors such as scavenger receptor BI (SR-BI), which mediate the selective uptake of cholesterol from ... reducing triglyceride synthesis and VLDL secretion through a receptor HM74 otherwise known as niacin receptor 2 and HM74A / ... Meyers CD, Carr MC, Park S, Brunzell JD (Dec 2003). "Varying cost and free nicotinic acid content in over-the-counter niacin ...
... nicotinic acetylcholine receptors more potently than n-methyl-D-aspartate receptors in rat hippocampal neurons". The Journal of ... It has been shown that the number of nicotinic receptors in the brain are reduced in Alzheimer's disease, even in the absence ... Memantine acts as a non-competitive antagonist at different neuronal nicotinic acetylcholine receptors (nAChRs) at potencies ... Buisson B, Bertrand D (March 1998). "Open-channel blockers at the human alpha4beta2 neuronal nicotinic acetylcholine receptor ...
Mefway for serotonin 5HT1A receptors, [18F] Nifene for nicotinic acetylcholine receptors or enzyme substrates (e.g. 6-FDOPA for ... Radioligands that bind to dopamine receptors (D1,[14] D2 receptor,[15][16] reuptake transporter), serotonin receptors (5HT1A, ... "Imaging cortical dopamine D1 receptors using 11C NNC112 and ketanserin blockade of the 5-HT 2A receptors". J Cereb Blood Flow ... Studies have been performed examining the state of these receptors in patients compared to healthy controls in schizophrenia, ...
The suppression of muscarinic receptors and the activation of nicotinic receptors due to prenatal exposure to nicotine have ... Acetylcholine plays an important modulatory role on the respiratory system by altering nicotinic and muscarinic receptors. ... Adenosine modulates the preBötC output via activation of the A1 and A2A receptor subtypes. An adenosine A1 receptor agonist has ... A lack of serotonin binding to the serotonin receptor 2 leads to the inability to autoresuscitation due to the lack of drive ...
Receptor/signaling modulators GABAA receptor positive modulators GABA metabolism/transport modulators ... GABA-A receptor activity. • transmembrane signaling receptor activity. • inhibitory extracellular ligand-gated ion channel ... Gamma-aminobutyric acid receptor subunit alpha-4 is a protein that in humans is encoded by the GABRA4 gene.[5][6] ... GABA-A receptor complex. • postsynaptic membrane. • membrane. • synapse. • integral component of plasma membrane. • chloride ...
Altinicline is a nicotinic acetylcholine receptor agonist that has shown potential in the treatment of Parkinson's disease, ... 3.0.CO;2-G. Parkinson Study, Group (14 February 2006). "Randomized placebo-controlled study of the nicotinic agonist SIB-1508Y ...
Glutamate receptor antagonist(英語:Excitatory amino acid antagonist) (NMDA(英語:NMDA receptor antagonist)) ... Nicotinic(英語:Nicotinic antagonist) (Ganglionic(英語:Ganglionic blocker). *神經肌肉阻滯藥)) ... Cannabinoid receptor antagonist(英語:Cannabinoid receptor antagonist). *Endocannabinoid enhancer(英語:Endocannabinoid enhancer) ( ... Glutamate receptor agonist(英語:Excitatory amino acid agonist) (AMPA(英語:Ampakine
The nerve tissues which communicate with muscles contain a receptor called the nicotinic acetylcholine receptor. Stimulation of ... The anatoxin-a molecule is shaped so it fits this receptor, and in this way it mimics the natural neurotransmitter normally ... and because it is a particularly useful molecule for investigating acetylcholine receptors in the nervous system.[1] The ... used by the receptor, acetylcholine. Once it has triggered a contraction, anatoxin-a does not allow the neurons to return to ...
Nicotinic acetylcholine receptor. Acetylcholine, Nicotine. Na+, K+, Ca2+[11]. Glycine receptor (GlyR). Glycine, Strychnine. Cl− ... GABA receptors: GABA-A, GABA-C. GABA. Cl− , HCO−3 [11]. Glutamate receptors: NMDA receptor, AMPA receptor, and Kainate receptor ... toll-like receptors (TLRs), killer activated and killer inhibitor receptors (KARs and KIRs), complement receptors, Fc receptors ... receptors, G protein-linked (metabotropic) hormone receptors, and enzyme-linked hormone receptors.[1] Intracellular receptors ...
See also: Receptor/signaling modulators • Nicotinic acetylcholine receptor modulators • Acetylcholine metabolism/transport ...
... mesylate (Corlopam) is a drug and synthetic benzazepine derivative which acts as a selective D1 receptor partial ... Grenader A, Healy DP (July 1991). "Fenoldopam is a partial agonist at dopamine-1 (DA1) receptors in LLC-PK1 cells". J. ... Hughes AD, Sever PS (1989). "Action of fenoldopam, a selective dopamine (DA1) receptor agonist, on isolated human arteries". ... D1 receptor stimulation activates adenylyl cyclase and raises intracellular cyclic AMP, resulting in vasodilation of most ...
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. ... regulation of receptor activity. • activation of phospholipase C activity. • neurotrophin TRK receptor signaling pathway. • ...
... activation of the D2 receptor promoter by members of the retinoic acid receptor-retinoid X receptor family". Proceedings of the ... 6-(N-ethyl-N-(5-isobutoxy-4-isopropyl-2-(E)-styrylphenyl)amino)nicotinic acid ... Isotretinoin has a low affinity for retinoic acid receptors (RAR) and retinoid X receptors (RXR), but may be converted ... transcriptional activation of the dopamine D2 receptor - in addition to serotonin and glutamate receptors - is regulated by ...
The LDL receptor gene is located on the short arm of chromosome 19 (19p13.1-13.3).[7] It comprises 18 exons and spans 45 kb, ... nicotinic acid preparations or fibrates.[2] Control of other risk factors for cardiovascular disease is required, as risk ... About 1 in 300 to 500 people have mutations in the LDLR gene that encodes the LDL receptor protein, which normally removes LDL ... Synthesis of cholesterol by the liver is suppressed in the HMG-CoA reductase pathway.[15] In FH, LDL receptor function is ...
Myasthenia gravis is caused by autoantibodies to the postsynaptic acetylcholine receptors. *Presynaptic terminal ...
... is a drug developed by Abbott, which acts as an agonist at neural nicotinic acetylcholine receptors selective for the ... See also: Receptor/signaling modulators • Muscarinic acetylcholine receptor modulators • Acetylcholine metabolism/transport ... "Central nicotinic receptors: structure, function, ligands, and therapeutic potential". ChemMedChem. 2 (6): 746-767. doi:10.1002 ... heptanes as Novel α4β2 Nicotinic Acetylcholine Receptor Selective Agonists". Journal of Medicinal Chemistry. 50 (22): 5493-5508 ...
... the neurotransmitter that inhibits cytokine release by interacting with alpha7 nicotinic acetylcholine receptors (CHRNA7) ... NOD-like receptor. References[edit]. *^ a b c d e f Janeway C, Travers P, Walport M, Shlomchik M (2001). Immunobiology (Fifth ... 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 ...
Suemaru K, Kohnomi S, Umeda K, Araki H. (2008). "Alpha7 nicotinic receptor agonists have reported to reverse the PPI disruption ... 2004). "Evidence of association between smoking and alpha7 nicotinic receptor subunit gene in schizophrenia patients". ... Gilbert Lagrue, François Lebargy, Anne Cormier, "From nicotinic receptors to smoking dependence: therapeutic prospects" ... posebej na nikotinske receptorje ganglijskega tipa ter na en nikotinski receptor CNS-a. Prvi je prisoten v nadledvičnem ...
The glycine receptor, alpha 4, also known as GLRA4, is a human pseudogene. The protein encoded by this gene is a subunit of the ... transmembrane signaling receptor activity. Cellular component. • integral component of membrane. • perikaryon. • postsynaptic ... "Structural analysis of mouse glycine receptor alpha subunit genes. Identification and chromosomal localization of a novel ...
See also: Receptor/signaling modulators • Nicotinic acetylcholine receptor modulators • Acetylcholine metabolism/transport ... σ1 receptor and D3 receptor agonist.[2] It produces antidepressant-like effects in rats.[2] However, captodiamine is unique ... enhances hypothalamic BDNF expression in vivo by synergistic 5-HT2c receptor antagonism and sigma-1 receptor agonism". J. ... In addition to its actions as an antihistamine, captodiamine has been found to act as a 5-HT2C receptor antagonist and ...
See also: Receptor/signaling modulators • Muscarinic acetylcholine receptor modulators • Nicotinic acetylcholine receptor ... Some noncholinergic mechanisms have also been proposed.[1] Donepezil upregulates the nicotinic receptors in the cortical ... σ1 receptor (Ki = 14.6 nM), and has been shown to produce specific antiamnestic effects in animals mainly via this action.[20] ... "The pharmacology of sigma-1 receptors". Pharmacology & Therapeutics. 124 (2): 195-206. doi:10.1016/j.pharmthera.2009.07.001 ...
Schneider, JS (2003). „The Subtype-Selective Nicotinic Acetylcholine Receptor Agonist SIB-1553A Improves Both Attention and ...
... which involves mutations in 2 nicotinic acetylcholine receptor genes. A genetic mutation on chromosome 22 has also been ...
September 2005). "Effects of quinine, quinidine, and chloroquine on alpha9alpha10 nicotinic cholinergic receptors". Molecular ...
Acetylcholine has been previously reported to enhance motility of this worm via nicotinic acetylcholine receptors.[21] ...
"Peer smoking and the nicotinic receptor genes: an examination of genetic and environmental risks for nicotine dependence". ...
See also: Receptor/signaling modulators • Nicotinic acetylcholine receptor modulators • Acetylcholine metabolism/transport ... Clidinium inhibits muscarinic acetylcholine receptors on smooth muscles, secretory glands, and in the central nervous system to ...
Diversity of mRNA expression for muscarinic acetylcholine receptor subtypes and neuronal nicotinic acetylcholine receptor ... Muskarinski acetilholinski receptor M3 (muskarinski holinergijski receptor 3) je muskarinski acetilholinski receptor. On je ... Kalcijum-detektujući receptor • GABA B (1, 2) • Glutamatni receptor (Metabotropni glutamat (1, 2, 3, 4, 5, 6, 7, 8)) • GPRC6A ... Acetylcholine receptors (muscarinic): M3". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and ...
Nicotine exerts its effects through the agonism of nicotinic acetylcholine receptor, resulting in multiple downstream effects ... as well as inhibit the inhibitory effect of adenosine receptors on dopamine receptors,[67] however the implications for humans ... Kamiya T, Saitoh O, Yoshioka K, Nakata H (June 2003). "Oligomerization of adenosine A2A and dopamine D2 receptors in living ... Adrenergic stimulants, such as ephedrine, may act by directly binding and activating the receptors that norepinephrine and ...
The N-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in ... The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA and kainate receptors. ... Receptor modulation[edit]. The NMDA receptor is a non-specific cation channel that can allow the passage of Ca2+ and Na+ into ... Na+, K+ and Ca2+ not only pass through the NMDA receptor channel but also modulate the activity of NMDA receptors.[citation ...
Briggs CA, McKenna DG (1996). „Effect of MK-801 at the human alpha 7 nicotinic acetylcholine receptor". Neuropharmacology. 35 ( ... NMDA receptor. Reference[уреди]. *^ Foster AC, Fagg GE (1987). „Neurobiology. Taking apart NMDA receptors". Nature. 329 (6138 ... Amador M, Dani JA (1991). „MK-801 inhibition of nicotinic acetylcholine receptor channels". Synapse. 7 (3): 207-15. PMID ... 1990). „The anticonvulsant MK-801 interacts with peripheral and central nicotinic acetylcholine receptor ion channels". The ...
The acetylcholine nicotinic receptor is an ionic channel whose aperture is directly controlled by acetylcholine. It is a key ... αBungarotoxin and Presynaptic Nicotinic Receptors: Functional Studies S. Wonnacott, J. Irons, G. G. Lunt, C. M. Rapier, E. X. ... Cholinergic Neuropathology and Nicotinic Receptor Binding in the Human Brain Elaine K. Perry, Carthage J. Smith, John H. Xuereb ... The acetylcholine nicotinic receptor is an ionic channel whose aperture is directly controlled by acetylcholine. It is a key ...
... Yue Zhao Center of Cell biology and Cancer Research, Albany ... Yue Zhao, "The Oncogenic Functions of Nicotinic Acetylcholine Receptors," Journal of Oncology, vol. 2016, Article ID 9650481, 9 ...
Zhao, Y., Liu, S., Zhou, Y. et al. Structural basis of human α7 nicotinic acetylcholine receptor activation. Cell Res 31, 713- ... 1: Cryo-EM structures of human α7 nicotinic receptor in different states.. ... Nicotinic acetylcholine receptors (nAChRs) are a class of pentameric ligand-gated ion channels (pLGICs) widely expressed in ... In conclusion, we present cryo-EM structures of the human α7 nicotinic receptor in apo-resting, agonist-bound desensitized, and ...
The technique was used to generate mice that express nicotinic receptors exclusively in the midbrain ventral tegmental area, ... Here we specifically re-expressed the β2-subunit of the nicotinic acetylcholine receptor (nAChR) by stereotaxically injecting a ... have developed an injectable lentiviral vector that delivers functional nicotinic acetylcholine receptors to defined regions of ... ligand-binding nicotinic acetylcholine receptors in dopamine-containing neurons of the VTA, together with the recovery of ...
... discovering a key factor in the development of addiction in nicotinic receptors. ... When nicotine enters the brain, it binds to nicotinic acetylcholine receptors (nAChRs) on the surface of neurons. Usually bound ... It is believed that any nicotine that has entered the cell can interact with these stored receptors though to what effect was ... Determining the pharmacokinetics of nicotinic drugs in the endoplasmic reticulum using biosensors. J. Gen. Physiol. doi:10.1085 ...
Nicotinic receptors are cells that respond to the neurotransmitters nicotine and acetylcholine. Once theyre triggered, they ... Nicotinic receptors are a type of acetylcholine receptor, which can also be called a cholinergic receptor. A receptor is a part ... Nicotinic receptors also fall under the category of an ionotropic receptor. An ionotropic receptor is a type of receptor that ... Cholinergenic receptors are sensitive to nicotine.. * Receptors -- such as nicotinic receptors -- are parts of cells that ...
Nicotinic acetylcholine receptors are the best-studied of the ionotropic receptors. Since nicotinic receptors help transmit ... The nicotinic receptors are considered cholinergic receptors, since they respond to acetylcholine. Nicotinic receptors get ... muscle-type nicotinic receptors and neuronal-type nicotinic receptors. In the muscle-type receptors, found at the neuromuscular ... Nicotinic receptors can also be found in different synaptic locations; for example the muscle nicotinic receptor always ...
ALPHA CHAINACETYLCHOLINE RECEPTOR PROTEIN, BETA CHAINACETYLCHOLINE RECEPTOR PROTEIN, DELTA CHAINACETYLCHOLINE RECEPTOR PROTEIN ...
α7 nicotinic acetylcholine receptor (α7nAChR) is a subtype of nAChR and has been reported to be involved in hypertension end- ... α7 Nicotinic Acetylcholine Receptor Relieves Angiotensin II-Induced Senescence in Vascular Smooth Muscle Cells by Raising ...
Lukas, R.J., et al., "Nicotinic acetylcholine receptors." in: The IUPHAR Compendium of Receptor Characterization and ... Postsynaptic receptors: synaptic transmission (rare), Presynaptic receptors extrasynaptic receptors: modulation of synaptic ... Hogg, R., et al., Nicotinic acetylcholine receptors as drug targets., Curr. Drug Targets CNS Neurol. Disord., 3, 123-130 (2004 ... Unwin, N., Structure and action of the nicotinic acetylcholine receptor explored by electron microscopy., FEBS Lett., 555, 91- ...
The muscle-type nicotinic receptor is a type of nicotinic acetylcholine receptor consisting of the subunit combination (α1)2 ... type nicotinic receptor. Since receptor activation occurs as isolated bursts, it has been proposed that the receptors have a ... α-Conotoxin Hexamethonium Pancuronium Tubocurarine Nicotinic acetylcholine receptor Ganglion type nicotinic receptor Rang HP, ... type nicotinic receptor. Benzocaine is a permanently uncharged species that inhibits the receptor by plugging the pore of the ...
acetylcholine receptor, nicotinic, alpha 5 (neuronal). cholinergic receptor, nicotinic alpha 5. cholinergic receptor, nicotinic ... CHRNA5 cholinergic receptor nicotinic alpha 5 subunit [Homo sapiens] CHRNA5 cholinergic receptor nicotinic alpha 5 subunit [ ... Activation of Nicotinic Acetylcholine Receptors, organism-specific biosystemNicotinic acetylcholine receptors (nAchR) are a ... Postsynaptic nicotinic acetylcholine receptors, organism-specific biosystemNicotinic acetylcholine receptors are found in the ...
Inhibition of α9α10 nicotinic acetylcholine receptors prevents chemotherapy-induced neuropathic pain. Haylie K. Romero, Sean B ... Inhibition of α9α10 nicotinic acetylcholine receptors prevents chemotherapy-induced neuropathic pain Message Subject (Your Name ... Antagonists of α9α10 nicotinic acetylcholine receptors (nAChRs) have been proposed as an important nonopioid mechanism based on ... We establish that a highly selective and potent inhibitor of the α9α10 nicotinic acetylcholine receptor (nAChR) subtype ...
Nicotinic acetylcholine receptor properties are modulated by surrounding lipids. An in vivo study ... Chol Acetylcholine Receptor Phosphatidic Acid Phosphatidic Acid Molecular Neuroscience Volume These keywords were added by ... Fong T. M. and McNamee M. G. (1986) Correlation between acetylcholine receptor function and structural properties of membranes ... Incorporation of reconstituted acetylcholine receptors from Torpedo into Xenopus oocyte membrane. Proc. Natl. Acad. Sci. U. S. ...
Nicotinic acetylcholine receptors, or nAChRs, are ionotropic receptors that form ligand-gated ion ... Cys-loop receptors. 5-HT receptor (5-HT3 serotonin receptor (A)) - GABA receptor (GABA A (α1, α2, α3, α5, α6, β1, β2, β3, γ2, ε ... Nicotinic receptors can also be found in different synaptic locations, for example the muscle nicotinic receptor always ... Nicotinic acetylcholine receptors, or nAChRs, are ionotropic receptors that form ligand-gated ion channels in cells plasma ...
Agrin causes acetylcholine receptors (AChRs) on chick myotubes in culture to aggregate, forming specializations that resemble ... Agrin induces phosphorylation of the nicotinic acetylcholine receptor Neuron. 1991 Jun;6(6):869-78. doi: 10.1016/0896-6273(91) ... Agrin causes acetylcholine receptors (AChRs) on chick myotubes in culture to aggregate, forming specializations that resemble ...
... binds to its nicotinic acteylcholine receptor (nAChR). I know that the nAChR has two alpha... ... Related Threads on Acetylecholine Binding to Nicotinic Acetylcholine Receptor What happens to molecules after binding to a ... Im a bit confused about the details of how actylcholine (ACh) binds to its nicotinic acteylcholine receptor (nAChR).. I know ... For the receptor to get activated, only one ACh will make 2 non-covalent bonds with 2 subunits of the receptor in question. ...
Nicotinic acetylcholine receptors (nAChRs) affect multiple physiological functions in the brain and their functions are ... Functional interaction between Lypd6 and nicotinic acetylcholine receptors J Neurochem. 2016 Sep;138(6):806-20. doi: 10.1111/ ... Nicotinic acetylcholine receptors (nAChRs) affect multiple physiological functions in the brain and their functions are ... Regulatory proteins of the Lynx family modulate the function of nicotinic receptors (nAChRs). We report for the first time that ...
Tests using mice employed an experimental drug that stimulates a specific type of nicotinic receptor in immune cells; ... Nicotinic receptor could be target for treatment of lung inflammation. Fundação de Amparo à Pesquisa do Estado de São Paulo ... Nicotinic receptor could be target for treatment of lung inflammation Tests using mice employed an experimental drug that ... Both nicotinic and muscarinic receptors are part of the cholinergic system, a branch of the nervous system in which ...
Nicotinic acetylcholine receptor expression by directionally selective ganglion cells - Volume 24 Issue 4 - CHRISTIANNE E. ... Lindstrom, J.M. (1996). Neuronal nicotinic acetylcholine receptors. In Ion Channels, Vol. 4, ed. Narahashi, T., pp. 377-449. ... Clementi, F., Fornasari, D. & Gotti, C. (2000). Neuronal nicotinic receptors, important new players in brain function. European ... Nicotinic acetylcholine receptor expression by directionally selective ganglion cells. * CHRISTIANNE E. STRANG (a1), JORDAN M. ...
The goal of this project is to identify abstinence-induced changes in neuronal nicotinic receptor availability that may ... Nicotine exerts its reinforcing properties, in part, by binding to α4β2* nicotinic acetylcholine receptors (nAChRs) in the ... study examines the effects of 24 hours abstinence from smoking on return to availability of neuronal nicotinic receptors in ... The 2-[18F]FA radiotracer allows us to measure nicotine receptors. The PET imaging technique used at these sessions allows us ...
"The role of estrogen receptor β and nicotinic cholinergic receptors in postpartum depression," Progress in Neuro- ... The Nicotinic Acetylcholine Receptor as a Target for Antidepressant Drug Development. Noah S. Philip, Linda L. Carpenter, ... Shafiqur Rahman, "Targeting brain nicotinic acetylcholine receptors to treat major depression and co-morbid alcohol or nicotine ... nicotinic acetylcholine receptors, in nonhuman primates," European Journal Of Nuclear Medicine And Molecular Imaging, vol. 43, ...
This receptor, known as the nicotinic acetylcholine receptor, increases excitability within the brains reward centers. Full ... Researchers discovered that the rats most likely to self-administer addictive drugs had a particular receptor in the brain that ... is more responsive than the same receptor in rats least likely to self-administer addictive drugs. ...
The nicotinic acetylcholine receptor protein. The nicotinic acetylcholine receptor protein contains a binding site(s) for the ... The nicotinic acetylcholine receptor was the first membrane receptor of a neurotransmitter and ion channel that was ... Dani JA, Bertrand D. Nicotinic acetylcholine receptors and nicotinic cholinergic mechanisms of the central nervous system. Annu ... "Nicotinic acetylcholine receptors" by Pierre-Jean Corringer and Jean-Pierre Changeux is licensed under a Creative Commons ...
Layer VI nicotinic currents are directly mediated by somatodendritic nicotinic receptors. The nicotinic inward currents in ... Developmental changes in layer VI nicotinic receptors. The presence of developmentally regulated nicotinic receptors in layer ... nicotinic receptors. There appears to be variability in the desensitization parameters of α4β2* nicotinic receptors (Quick and ... Layer VI nicotinic currents are mediated by α4β2* nicotinic receptors. We found that the competitive α4β2* antagonist DHβE (3 ...
... channels as well as nicotinic acetylcholine receptors (nAChRs) which are classified as ligand-gated ion channels. The mode of ... Conotoxins Targeting Nicotinic Acetylcholine Receptors: An Overview by Eline K. M. Lebbe. , Steve Peigneur. , Isuru Wijesekara ... Keywords: nicotinic acetylcholine receptor; cone snail toxins; α-conotoxins; mode of action; working mechanism; acetylcholine ... "Conotoxins Targeting Nicotinic Acetylcholine Receptors: An Overview." Mar. Drugs 12, no. 5: 2970-3004. ...
... is a novel agonist for nicotinic acetylcholine receptors (nAChRs). We examined its efficacy, affinity, and potency for α6β2* ( ... E)-5-(Pyrimidin-5-yl)-1,2,3,4,7,8-hexahydroazocine (TC299423) is a novel agonist for nicotinic acetylcholine receptors (nAChRs ... 2008). Upregulation of nicotinic receptors by nicotine varies with receptor subtype. J. Biol. Chem. 283, 6022-6032. doi: ... 2014). α6β2∗-subtype nicotinic acetylcholine receptors are more sensitive than α4β2∗-subtype receptors to regulation by chronic ...
Goat polyclonal Nicotinic Acetylcholine Receptor beta 2 antibody validated for WB and tested in Human. Immunogen corresponding ... Anti-Nicotinic Acetylcholine Receptor beta 2 antibody. See all Nicotinic Acetylcholine Receptor beta 2 primary antibodies. ... Cholinergic receptor nicotinic beta polypeptide 2 antibody. *Cholinergic receptor nicotinic beta polypeptide 2 neuronal ... Anti-Nicotinic Acetylcholine Receptor beta 2 antibody (ab85693) at 1 µg/ml + Human cerebellum lysate (in RIPA buffer) at 35 µg ...
References for Abcams Anti-Nicotinic Acetylcholine Receptor beta antibody (ab66429). Please let us know if you have used this ...
... nicotinic, alpha 2 (neuronal) Biomolecules from leading suppliers on Biocompare. View specifications, prices, citations, ... Your search returned 2 cholinergic receptor, nicotinic, alpha 2 (neuronal) Biomolecules across 1 supplier. ... cholinergic receptor, nicotinic, alpha 2 (neuronal) Biomolecules. cholinergic receptor, nicotinic, alpha 2 (neuronal) ...
  • Nicotinic acetylcholine receptors (nAChRs) are a class of pentameric ligand-gated ion channels (pLGICs) widely expressed in nervous system. (nature.com)
  • nAChRs function as neurotransmitter receptors that respond to endogenous acetylcholine and choline, modulating neuronal excitability and synaptic communication. (nature.com)
  • When nicotine enters the brain, it binds to nicotinic acetylcholine receptors (nAChRs) on the surface of neurons. (biotechniques.com)
  • Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. (wikipedia.org)
  • As ionotropic receptors, nAChRs are directly linked to ion channels. (wikipedia.org)
  • 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 of α7 receptors. (wikipedia.org)
  • Nicotinic acetylcholine receptors (nAChRs) constitute a family of ligand-gated channels, originally classified on the basis of their activation by the alkaloid nicotine, with acetylcholine (ACh) being the endogenous ligand. (sigmaaldrich.com)
  • Nicotinic acetylcholine receptors , or nAChRs , are ionotropic receptors that form ligand-gated ion channels in cells' plasma membranes . (bionity.com)
  • Nicotinic acetylcholine receptors (nAChRs) affect multiple physiological functions in the brain and their functions are modulated by regulatory proteins of the Lynx family. (nih.gov)
  • Regulatory proteins of the Lynx family modulate the function of nicotinic receptors (nAChRs). (nih.gov)
  • Neuronal nicotinic AChRs (nAChRs) are implicated in the pathogenesis of diverse neurological disorders and in the regulation of small-cell lung carcinoma growth. (jci.org)
  • In contrast to α2βγδ muscle-type nAChR, the simplest receptors are homo-pentameric nAChRs made up of α7-10 subunits with a perfect five-fold symmetry. (scholarpedia.org)
  • Cone snail venom comprises of a rich and diverse cocktail of peptide toxins which act on a wide variety of ion channels such as voltage-gated sodium- (Na V ), potassium- (K V ), and calcium- (Ca V ) channels as well as nicotinic acetylcholine receptors (nAChRs) which are classified as ligand-gated ion channels. (mdpi.com)
  • E)-5-(Pyrimidin-5-yl)-1,2,3,4,7,8-hexahydroazocine (TC299423) is a novel agonist for nicotinic acetylcholine receptors (nAChRs). (frontiersin.org)
  • it is mediated by acetylcholine activating nicotinic acetylcholine receptors (nAChRs) that generate waves of activity across brain regions. (jneurosci.org)
  • Similarly, nicotinic activation of α7-nAChRs in WT organotypic culture, as well as cell culture, increases the number of glutamatergic synapses. (jneurosci.org)
  • Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that consist of pentameric combinations of α and β subunits. (aspetjournals.org)
  • 2009 ). The attempts to isolate the physiologic effect of nicotinic acetylcholine receptors (nAChRs) using the Torpedo organism have been traced back as far as 1885 (Paul Ehrlich) and 1857 (Claude Bernard). (springer.com)
  • Today nAChRs are considered prototypes of receptors that function as integral signal transducers. (intechopen.com)
  • 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. (bl.uk)
  • This smoking addiction results from nicotine acting on neuronal nicotinic acetylcholine receptors (nAchRs) in the brain in key regions controlling behavior. (jci.org)
  • Beside the role in inflammation there is evidence that neuronal nicotinic acetylcholine receptors (nAChRs) may modulate other neuronal activities within the central nervous system (CNS) and may have a distinct role in regulating neuronal growth and differentiation in developing CNS. (wingsforlife.com)
  • Nicotine acts in the brain through the neuronal nicotinic acetylcholine receptors (nAChRs), which are ligand-gated ion channels consisting of five membrane-spanning subunits 3 . (pubmedcentralcanada.ca)
  • Acetylcholine release in sensory neocortex contributes to higher-order sensory function, in part by activating nicotinic acetylcholine receptors (nAChRs). (ed.gov)
  • α7 nicotinic acetylcholine receptors (nAChRs) play an important role in synaptic transmission and inflammation. (wingsforlife.com)
  • In the present study, the efficacy and potency of mecamylamine and its stereoisomers were evaluated as inhibitors of human α3β4, α3β2, α7, and α4β2 nicotinic acetylcholine receptors (nAChRs), as well as mouse adult type muscle nAChRs and rat N -methyl- d -aspartate (NMDA) receptors expressed in Xenopus oocytes. (aspetjournals.org)
  • Mecamylamine is widely used as a broad-spectrum antagonist of neuronal nicotinic acetylcholine (ACh) receptors (nAChRs) and, despite its common usage, questions still exist as to its precise specificity and mechanisms of action. (aspetjournals.org)
  • Subsequent work with knockout mice demonstrated that α6β2* nicotinic receptors (nAChRs) play a key role. (sri.com)
  • Inflammatory and structural cells involved in the pathophysiology of asthma express a variety of receptors, including nicotinic acetylcholine receptors (nAChRs) 5 - 7 . (ersjournals.com)
  • Activation of nicotinic acetylcholine receptors (nAChRs) by nicotine or specific alpha 7 nAChR agonists reduces neuroinflammation. (diva-portal.org)
  • Some heteropentameric nicotinic acetylcholine receptors (nAChRs) are up-regulated by chronic nicotine. (caltech.edu)
  • 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. (open.ac.uk)
  • Morphological considerations and double immunolabeling indicate that GABAergic as well as glutamatergic synapses bear 7 nAChRs, at densities approaching those observed for glutamate receptors in CA1 stratum radiatum. (open.ac.uk)
  • On the basis of their ligand-binding properties, nicotinic acetylcholine receptor (nAChRs) are divided into two classes: (1) α-bungarotoxin (α-Bgtx)-binding nAChRs containing α7 or α9 subunits, which form homopentamers, and (2) α-Bgtx nonbinding nAChRs containing α2-α6 and β2-β4 subunits, which form heteromeric receptors with high affinities for receptor agonists such as acetylcholine and nicotine ( 1, 2 ). (aacrjournals.org)
  • The nicotinic agonists at the top of the signaling cascades are listed in the order of their affinity for nAChRs. (aacrjournals.org)
  • To identify the molecular determinants responsible for lidocaine blockade of muscle-type nAChRs, we have studied the effects on this receptor of 2,6-dimethylaniline (DMA), which resembles lidocaine's hydrophobic moiety. (frontiersin.org)
  • This is particularly true for nicotinic acetylcholine receptors (nAChRs), a class of pentameric ligand-gated ion channels. (une.edu)
  • We have demonstrated these soluble pentameric proteins share considerable homology with human nAChRs and present a ligand binding profile similar to that observed for wild type receptors. (une.edu)
  • The expressions of nicotinic acetylcholine receptors (nAChRs) at protein and mRNA levels were detected by Western blotting and Real-time PCR, respectively. (fluoridealert.org)
  • Activation of both alpha7 and beta2(*) nicotinic acetylcholine receptors (nAChRs) in the prefrontal cortex (PFC) has been implicated in these processes. (unboundmedicine.com)
  • 5 γ-Aminobutyric acid type A (GABA A ) receptors and neuronal nicotinic acetylcholine receptors (nAChRs) have been implicated in the mechanism of action of both intravenous and gaseous general anesthetics. (asahq.org)
  • Volatile anesthetics inhibit heteromeric nAChRs more potently than homomeric receptors composed of the α 7 subunit, 7,8 whereas thiopental and ketamine inhibit both types of nAChRs approximately equipotently. (asahq.org)
  • 16 As such, we tested the rat α 1 β 1 γ 2 GABA A receptor and the human α 7 and α 4 β 2 nAChRs, expressed in Xenopus oocytes, for modulation by droperidol. (asahq.org)
  • Here we specifically re-expressed the β2-subunit of the nicotinic acetylcholine receptor (nAChR) by stereotaxically injecting a lentiviral vector into the VTA of mice carrying β2-subunit deletions 3 , 4 . (nature.com)
  • α7 nicotinic acetylcholine receptor (α7nAChR) is a subtype of nAChR and has been reported to be involved in hypertension end-organ damage. (ingentaconnect.com)
  • These are the most divergent of the nAChR family and show mixed nicotinic/muscarinic pharmacology, and sensitivity to other drugs including strychnine and 5HT 3 ligands. (sigmaaldrich.com)
  • The frog alkaloid epibatidine is one of the most potent nicotinic agonists (K i ~50 pM for binding to a4b2 nAChR) and is 100-fold more potent than morphine as an analgesic. (sigmaaldrich.com)
  • We establish that a highly selective and potent inhibitor of the α9α10 nicotinic acetylcholine receptor (nAChR) subtype prevents the expression of chemotherapy-induced neuropathic pain. (pnas.org)
  • I'm a bit confused about the details of how actylcholine (ACh) binds to its nicotinic acteylcholine receptor (nAChR). (physicsforums.com)
  • The nicotinic acetylcholine receptor (nAChR), a key player in neuronal communication, converts neurotransmitter binding into membrane electrical depolarization. (scholarpedia.org)
  • Led by Steven DeKosky at the University of Pittsburgh School of Medicine in Pennsylvania, who since moved to become dean of the University of Virginia School of Medicine, researchers report that α7 nicotinic acetylcholine receptor (nAChR) levels in the superior frontal cortex remain stable during the transition from normal cognition to mild AD, even as Aβ peptide concentrations rise. (alzforum.org)
  • Albeit with modest sample size, the study calls into question earlier observations of waning brain α7 nAChR expression in AD, and bears out the idea that this receptor holds promise as an AD drug target. (alzforum.org)
  • Alongside the earlier studies showing decreased expression of this receptor in AD brains, some analyses have found that α7 nAChR levels remain stable (e.g. (alzforum.org)
  • Nicotinic acetylcholine receptors (nAChR) are the archetypes of drug receptors. (intechopen.com)
  • The neurotransmitter acetylcholine binds to the extracellular domain of the nAChR and, consequently, opens the receptor-integral membrane channel for Na + , K + and Ca 2+ ions. (intechopen.com)
  • A particularly close relationship between 5-HT 3 R and nicotinic acetylcholine receptors (nAChR) has been demonstrated by the construction of a functional chimeric receptor, containing the ligand-binding domain of the nAChR α7 and the ion channel domain of the 5-HT 3 R subunits ( 10 ). (pnas.org)
  • Because of the close resemblance between 5-HT 3 and nAChR subunits, we examined whether the 5-HT 3 R subunit can coassemble with nAChR subunits to form heteromeric receptors. (pnas.org)
  • Chimeric receptor constructs and site‐directed mutagenesis studies, together with ligand docking simulations, have highlighted the importance of the transmembrane region of the α7 nAChR for modulation by these ligands. (bl.uk)
  • Nicotinic receptors (nAChR) are acetylcholine-activated non-selective cation channels that mediate excitatory neurotransmission. (criver.com)
  • The human CHRNA3 and CHRNB4 genes encode a cationic-selective, ionotropic α3/β4/α5 nicotinic acetylcholine receptor (nAChR). (criver.com)
  • The first part of this dissertation is focused on the design and synthesis of molecules that differentially regulate activation and desensitization of the human alpha7 nicotinic acetylcholine receptor (nAChR). (ufl.edu)
  • Genetic variation in CHRNA5 , the gene encoding the α5 nicotinic acetylcholine receptor (nAChR) subunit, increases vulnerability to tobacco addiction and lung cancer, but underlying mechanisms are unknown. (pubmedcentralcanada.ca)
  • 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)
  • The nicotinic acetylcholine receptor, nAChR a6/3β2β3 forms a ligand-gated, heteropentameric, cation-selective channel which modulates neurotransmission in the nervous system. (criver.com)
  • A potent (inhibition constant = 37 picomolar) neuronal nicotinic acetylcholine receptor (nAChR) ligand called ABT-594 was developed that has antinociceptive properties equal in efficacy to those of morphine across a series of diverse animal models of acute thermal, persistent chemical, and neuropathic pain states. (sciencemag.org)
  • Voltage-clamp recordings in Xenopus oocytes revealed that 20-meSPX-G potently inhibited currents evoked by ACh on Torpedo muscle-type and human α7 nicotinic acetylcholine receptors (nAChR), whereas lower potency was observed in human α4β2 nAChR. (mdpi.com)
  • The neuromuscular nicotinic acetylcholine receptor (nAChR) is the prototypic member of the pentameric ligand-gated ion channel (pLGIC) superfamily, a superfamily of neurotransmitter receptors that plays a central role in information processing in the brain. (omicsonline.org)
  • His research is focused on understanding the mechanisms by which lipids influence nicotinic acetylcholine receptor structure and function in both normal and diseased states, with increasing focus on how lipid-nAChR interactions participate in congenital myasthenic syndromes. (omicsonline.org)
  • The beta 2 -* containing nicotinic acetylcholine receptor (β 2 *-nAChR) has recently emerged as a prime candidate because some alpha and beta subunit genes have been linked to alcohol consumption and alcohol use behaviors. (pubmedcentralcanada.ca)
  • In addition, α7- and α9-nAChR receptors have unique properties pertaining to the regulation of signaling mechanisms found in sensory epithelia (α7-nAChR) and other nonneuronal (α9-nAChR) cell types. (aacrjournals.org)
  • The nicotinic acetylcholine receptor (nAChR) is the prototypical member of the ligand-gated ion channel (LGIC) superfamily. (frontiersin.org)
  • The nAChR subtypes share considerable structural and sequence identity with each other and with related receptors. (une.edu)
  • The alpha7 nAChR ligand alpha-bungarotoxin and ryanodine receptors were colocalized to a subpopulation of PFC synaptosomes. (unboundmedicine.com)
  • The expression vectors for receptor subtype cDNAs were as follows: pSP64 for the human α 4 and β 2 type nAChR, pMXT for the α 7 type nAChR, pGEMHE for the rat GABA α 1 and γ 2 , and pGEMVE for the rat GABA β 1 . (asahq.org)
  • The nicotinic acetylcholine receptor (nAChR) is a ligand-gated ion channel that switches upon activation from a closed state to a full conducting state. (epfl.ch)
  • We demonstrate the efficient re-expression of electrophysiologically responsive, ligand-binding nicotinic acetylcholine receptors in dopamine-containing neurons of the VTA, together with the recovery of nicotine-elicited dopamine release and nicotine self-administration. (nature.com)
  • Abnormal avoidance learning in mice lacking functional high-affinity nicotine receptor in the brain. (nature.com)
  • Acetylcholine receptors containing the β2 subunit are involved in the reinforcing properties of nicotine. (nature.com)
  • It is believed that any nicotine that has entered the cell can interact with these stored receptors though to what effect was previously unknown. (biotechniques.com)
  • Also called nicotinic acetylcholine receptors, nicotinic receptors are cells that respond to nicotine , a neurotransmitter. (wisegeek.com)
  • In addition to nicotine, the action of nicotinic receptors is triggered by acetylcholine (ACh), another common neurotransmitter. (wisegeek.com)
  • When nicotine triggers nicotinic receptors, its molecules are considered to be ligands, or types of molecules that trigger receptors. (wisegeek.com)
  • Though muscarinic receptors primarily respond to muscarine, they do also respond to nicotine to a lesser degree. (wisegeek.com)
  • Would it be possible to somehow treat the nicotonic receptors so that they did not respond to nicotine as well as they do naturally? (wisegeek.com)
  • Nicotinic receptors also respond to drugs such as the agonist nicotine. (wikipedia.org)
  • Nicotinic receptors get their name from nicotine which does not stimulate the muscarinic acetylcholine receptors but selectively binds to the nicotinic receptors instead. (wikipedia.org)
  • Like the other type of acetylcholine receptors , muscarinic acetylcholine receptors (mAChRs), their opening is triggered by the neurotransmitter acetylcholine (ACh), but they are also opened by nicotine . (bionity.com)
  • This activation of receptors by nicotine modifies the state of neurons through two main mechanisms. (bionity.com)
  • This positron emission tomography (PET) study examines the effects of 24 hours abstinence from smoking on return to availability of neuronal nicotinic receptors in slow and fast metabolizers of nicotine. (clinicaltrials.gov)
  • The 2-[18F]FA radiotracer allows us to measure nicotine receptors. (clinicaltrials.gov)
  • The PET imaging technique used at these sessions allows us to measure the amount of light that 2-[18F]FA gives off in different regions of the brain, we can estimate how many nicotine receptors are in that region. (clinicaltrials.gov)
  • Finally, we examined the effects of the drug nicotine on layer VI neurons and probed for the potential involvement of the accessory subunit, α 5 , in their receptors. (jneurosci.org)
  • Understanding the properties of nicotinic currents in layer VI neurons is critical to appreciate the potential trophic effects of acetylcholine on these neurons and how they may be altered by exposure to the drug nicotine during development. (jneurosci.org)
  • They found that inactivation of beta2 subunit, a specific sub-class of nicotinic receptors that bind nicotine, appears to reduce anxiety. (thefreedictionary.com)
  • Nicotine is a naturally occurring alkaloid that is capable of stimulating acetylcholine receptors in both the sympathetic and parasympathetic systems, as well as cholinergic nicotinic receptors at skeletal muscle sites and in the brain. (thefreedictionary.com)
  • Nakayama H, Shimoke K, Isosaki M, Satoh H, Yoshizumi M, Ikeuchi T. Subtypes of neuronal nicotinic acetylcholine receptors involved in nicotine-induced phosphorylation of extracellular signal-regulated protein kinase in PC12h cells. (springer.com)
  • Effect of nicotine and nicotinic receptors on anxiety and depression. (springer.com)
  • Although pain, memory and nicotine addiction may not seem to be related, they actually share a common player: the nicotinic acetylcholine receptors. (medicalxpress.com)
  • Menthol acts in combination with nicotine to desensitize the type of nicotinic receptors found in lungs and airways that are responsible for nicotine's irritation, say Georgetown University Medical Center (GUMC) researchers. (medicalxpress.com)
  • By stimulating cold and nicotine receptors, researchers successfully improved metabolism in mice, helping them to lose weight. (neurosciencenews.com)
  • A detailed 3D structure of nicotinic acetylcholine receptors could help pave the way to developing new treatments for nicotine addiction, researchers report. (neurosciencenews.com)
  • For example, long-term exposure to nicotine leads to long-lasting changes in both the abundance and functional activity of nicotinic receptors in brain neurons, processes thought to be critical for nicotine addiction ( D ani and H einemann 1996 ). (genetics.org)
  • They are also the receptors that mediate the effects of tobacco smoking and contribute to the physiological and psychological changes associated with nicotine addiction. (bl.uk)
  • By introducing a specific marker and using fish electric organ, a type of tissue that is abundant in cholinergic synapses [as demonstrated by David Nachmansohn in 1936 while working in Paris] it was possible to isolate the nicotine receptor studied by Langley. (pasteur.fr)
  • Because mecamylamine, a nicotinic receptor antagonist, is used so often in nicotine research and because mecamylamine may have important therapeutic properties clinically, it is important to fully explore and understand its pharmacology. (aspetjournals.org)
  • Since nicotine has both agonist and antagonistic properties, nicotinic receptor antagonists, such as mecamylamine, may also be useful for a wide range of nicotine-responsive neuropsychiatric disorders. (aspetjournals.org)
  • In animal models, nicotine, a nicotinic receptor agonist, inhibits the development of inflammatory diseases such as type I diabetes 8 and hypersensitivity pneumonitis 9 . (ersjournals.com)
  • Nicotine also blocks lymphocytes in the G0/G1 phase of the cell cycle and affects the intracellular signalling cascade activated by the stimulation of the T-cell receptor 12 . (ersjournals.com)
  • These data revealed that nicotine and NNK are two major components in cigarette smoke that are responsible for the tumor promoting effects on gastric carcinogenesis through the cooperation of different receptors to regulate the progression of cell cycle via COX-2 dependent pathway. (aacrjournals.org)
  • We have developed a novel technique of quantifying nicotinic acetylcholine receptor changes within subcellular regions of specific subtypes of CNS neurons to better understand the mechanisms of nicotine addiction by using a combination of approaches including fluorescent protein tagging of the receptor using the knock-in approach and spectral confocal imaging. (jove.com)
  • Nicotinic receptors, with a molecular mass of 290 kDa, are made up of five subunits, arranged symmetrically around a central pore. (wikipedia.org)
  • The neuronal subtypes are various homomeric (all one type of subunit) or heteromeric (at least one α and one β) combinations of twelve different nicotinic receptor subunits: α2−α10 and β2−β4. (wikipedia.org)
  • In both muscle-type and neuronal-type receptors, the subunits are very similar to one another, especially in the hydrophobic regions. (wikipedia.org)
  • α1, β1, γ, δ and ε subunits are only expressed in skeletal muscle, whereas the other subunits are found mainly in neurons (hence "neuronal nicotinic receptors") but also in other cell types. (sigmaaldrich.com)
  • These receptors are thought to be heteropentamers composed of separate but similar subunits. (nih.gov)
  • Twelve types of nicotinic receptor subunits, α2 through 10 and β2 through 4 (Itier and Bertrand, 2001), combine to form pentamers. (bionity.com)
  • For the receptor to get activated, only one ACh will make 2 non-covalent bonds with 2 subunits of the receptor in question. (physicsforums.com)
  • The muscle/electric organ nicotinic acetylcholine receptor is composed of four different types of subunits, named α1, β1, γ1 and δ1 according to their apparent molecular weight, that associate into a pentamer with an α2βγδ stoichiometry and a (αγαδβ) organisation. (scholarpedia.org)
  • Neuronal nicotinic receptors are made up of different subunits associated in a variety of combinations. (scholarpedia.org)
  • In contrast, known 5-HT 3 R subunits are all homologs of the same 5-HT 3 R-A subunit and form homopentameric receptors. (pnas.org)
  • Here we show, by heterologous expression followed by immunoprecipitation, that 5-HT 3 R and nicotinic acetylcholine receptor α4 subunits coassemble into a novel type of heteromeric ligand-gated ion channel, which is activated by 5-HT. (pnas.org)
  • Coassembly of subunits beyond the boundaries of ligand-gated ion channel families may constitute an important mechanism contributing to the diverse properties and functions of native neurotransmitter receptors. (pnas.org)
  • In heterologous expression systems, the coassembly of related subunits permits formation of a vast repertoire of neurotransmitter receptors, each with its own characteristic properties. (pnas.org)
  • A focus in contemporary neuroscience is to understand the functional significance of the variety of cloned subunits for the diverse properties and functions of native neurotransmitter receptors. (pnas.org)
  • For serotonin (5-hydroxytryptamine) type 3 receptors (5-HT 3 R), little molecular diversity has become apparent: only a single class of 5-HT 3 R subunit has been cloned ( 1 - 3 ), and these subunits form homomeric receptors with similar functional properties in heterologous expression systems ( 4 , 5 ). (pnas.org)
  • Conversely, studies of native receptors, indicating substantial heterogeneity of 5-HT 3 R properties, suggest the existence of additional subunits involved in the formation of heteromeric 5-HT 3 Rs ( 6 - 9 ). (pnas.org)
  • unc-29 and lev-1 encode candidate non-α-subunits of the levamisole receptor, whereas unc-38 encodes a candidate α-subunit. (genetics.org)
  • Marubio LM, del Mar Arroyo-Jimenez M, Cordero-Erausquin M, Lena C, Le Novere N, de Kerchove d'Exaerde A, Huchet M, Damaj MI, Changeux JP (1999) Reduced antinociception in mice lacking neuronal nicotinic receptor subunits. (springer.com)
  • Data for wild-type receptors from monomeric subunits in Fig. 1 are indicated as dashed lines. (rupress.org)
  • Several different terms are used to refer to the molecules that bind receptors, such as ligand, agonist, or transmitter. (wikipedia.org)
  • Tetraethylammonium (TEA) is a molecule found to be a weak agonist of the muscle‐type nicotinic receptor. (wikipedia.org)
  • It has been reported that prolonged exposure to the agonist receptor itself causes an agonist-induced conformational change in the receptor, resulting in receptor desensitization. (bionity.com)
  • BOSTON -- An investigational nicotinic receptor agonist demonstrated cognitive benefits similar to those seen with donepezil in a phase II trial of patients with mild to moderate Alzheimer's disease. (thefreedictionary.com)
  • The recent identification of the Gi-coupled protein receptor HCAR2, for which NA is a potent agonist, provides intriguing insight due to its anti-lipolytic action and restricted, yet specific, expression in adipose tissue and immune cells. (bl.uk)
  • A nicotinic acetylcholine receptor agonist, imidacloprid, impairs memory formation in honey bees and has general effects on foraging. (biologists.org)
  • Here, studying (α4) 3 (β2) 2 receptors, we show that mutations at either the principal face of the β2 subunit or the complementary face of the α4 subunit prevent NS9283 potentiation of ACh-elicited single-channel currents, suggesting the drug targets the β2-α4 pseudo-agonist sites, the α4-α4 agonist site, or both sites. (springer.com)
  • Thus, monitoring potentiation of single concatemeric receptor channels reveals that the β2-α4 pseudo-agonist sites are required for stoichiometry-selective drug action. (springer.com)
  • However, both receptors were phosphorylated in an agonist-dependent manner. (gla.ac.uk)
  • This study provides the first substantive clinical evidence that compounds where the primary pharmacology is antagonism to neuronal nicotinic receptors will have antidepressant properties," said Dr. (thefreedictionary.com)
  • The nicotinic acetylcholine receptor α4 subunit page is available on the IUPHAR/BPS Guide to PHARMACOLOGY site. (iuphar-db.org)
  • Frequency of the cholinergic receptor nicotinic alpha 5 (CHRNA5) rs16969968-A allele and cholinergic receptor nicotinic alpha 3 (CHRNA3) rs1051730-T allele were significantly higher in lung cancer than in normal controls. (nih.gov)
  • Your search returned 2 cholinergic receptor, nicotinic, alpha 2 (neuronal) Biomolecules across 1 supplier. (biocompare.com)
  • Your search returned 49 cholinergic receptor nicotinic alpha 1 subunit ELISA ELISA Kit across 6 suppliers. (biocompare.com)
  • Auf www.antikoerper-online.de finden Sie aktuell 72 Cholinergic Receptor, Nicotinic, alpha 3 (Neuronal) (CHRNA3) Antikörper von 17 unterschiedlichen Herstellern. (antikoerper-online.de)
  • Zusätzlich bieten wir Ihnen Cholinergic Receptor, Nicotinic, alpha 3 (Neuronal) Proteine (10) und Cholinergic Receptor, Nicotinic, alpha 3 (Neuronal) Kits (5) und viele weitere Produktgruppen zu diesem Protein an. (antikoerper-online.de)
  • Insgesamt sind aktuell 94 Cholinergic Receptor, Nicotinic, alpha 3 (Neuronal) Produkte verfügbar. (antikoerper-online.de)
  • 5 PNU-120596 (abbreviated as PNU) is the first reported α7-selective PAM that could increase the peak current of the receptor evoked by agonists and delay channel desensitization. (nature.com)
  • The term "silent agonists" is introduced to describe receptor ligands that bind to the conventional acetylcholine binding site, do not initiate ion channel activity, and place the receptor in a desensitized state that can be revealed in the presence of a type II positive allosteric modulator. (ufl.edu)
  • Nicotinic agonists, including 1,1-dimethyl-4-phenylpiperazinium (DMPP), have anti-inflammatory properties and in some instances smooth muscle relaxing effects. (ersjournals.com)
  • Nicotinic agonists have anti-inflammatory effects both in vitro and in vivo . (ersjournals.com)
  • At the neuromuscular junction they are the primary receptor in muscle for motor nerve-muscle communication that controls muscle contraction. (wikipedia.org)
  • These receptors are found in neuromuscular junctions, where activation leads to an excitatory postsynaptic potential (EPSP), mainly by increased Na+ and K+ permeability. (wikipedia.org)
  • Agrin causes acetylcholine receptors (AChRs) on chick myotubes in culture to aggregate, forming specializations that resemble the postsynaptic apparatus at the vertebrate skeletal neuromuscular junction. (nih.gov)
  • In muscle cells, nicotinic receptors present at the neuromuscular junction mediate rapid excitation that leads to muscle contraction. (genetics.org)
  • The nicotinic receptors are cylindrically-shaped proteins imbedded in synaptic walls that act as chemically-controlled sodium channels (also called ligand-gated sodium channels) that penetrate through the cell walls of post-synaptic nerves and myocytes at the skeletal neuromuscular junctions. (cdc.gov)
  • In 1905, the British physiologist John Newport Langley demonstrated that curare acts on the muscle side of the neuromuscular junction in a structure that he described as a 'receptive substance' or receptor. (pasteur.fr)
  • McGehee, D. S. & Role, L. W. Physiological diversity of nicotinic acetylcholine receptors expressed by vertebrate neurons. (nature.com)
  • Diversity of nicotinic acetylcholine receptors in rat hippocampal neurons. (cambridge.org)
  • In this study, we show robust nicotinic excitation of pyramidal neurons in layer VI of prefrontal cortex. (jneurosci.org)
  • These experiments showed that layer VI neurons have peak nicotinic currents during the first postnatal month, a time period of intensive cortical development in rodents. (jneurosci.org)
  • As hypothesized, recordings from these retrogradely labeled neurons in layer VI showed prominent nicotinic currents. (jneurosci.org)
  • In summary, we show that layer VI corticothalamic neurons can be strongly excited during development by an unusual subtype of nicotinic receptor. (jneurosci.org)
  • We present here the first electrophysiological study of nicotinic currents in layer VI pyramidal cells and identified corticothalamic neurons during postnatal development. (jneurosci.org)
  • Neurons also contain nicotinic receptors, which are widely expressed in the brain and other neural tissues, and function in the modulation of neurotransmission ( S argent 1995 ). (genetics.org)
  • Allosteric modulation of nicotinic acetylcholine receptors. (springer.com)
  • 9-15 Modulation of GABA A receptors by general anesthetics is not particularly dependent on subunit composition. (asahq.org)
  • Targacept's product candidates selectively modulate neuronal nicotinic receptors that serve as key regulators of the nervous system to promote therapeutic effects and limit adverse side effects. (thefreedictionary.com)
  • This phenomenon is a part of a broader cholinergic anti-inflammatory pathway which activates the vagus nerve to modulate inflammation through activation of alpha7 nicotinic acetylcholine receptors (α7nACHR). (psu.edu)
  • In this case, the therapeutic effect is associated with activation of nicotinic receptors of the alpha-7 subtype in macrophages, the immune system's first-line cells that are central to the inflammatory response to a potential threat. (eurekalert.org)
  • Although there was little difference between S -(+)-mecamylamine and R -(−)-mecamylamine in terms of 50% inhibition concentration values for a given receptor subtype, there appeared to be significant differences in the off-rates for the mecamylamine isomers from the receptors. (aspetjournals.org)
  • Each receptor subtype has distinct electrophysiological and pharmacological properties. (aacrjournals.org)
  • Structural and molecular modeling features of P2X receptors. (springer.com)
  • Yet the molecular mechanisms responsible for regulating nicotinic receptor activity are not well understood in any organism. (genetics.org)
  • with its simple well-characterized nervous system and its amenability to classical and molecular genetic studies, is well suited for investigating how specific neurotransmitters, receptors, and signaling molecules function within the context of the nervous system to produce behavior. (genetics.org)
  • For those interested in learning about the molecular physiology of nicotinic receptors, the subject is discussed as optional reading below. (cdc.gov)
  • Despite its widespread availability and clinical use, the clinical target and precise molecular mechanism by which nicotinic acid acts remains elusive. (gla.ac.uk)
  • In order to maximise nicotinic acid's full potential as a lipid-modulating drug, overcome its related side effects and further develop novel and more potent drugs it is vital to understand its molecular mechanism of action. (gla.ac.uk)
  • In vertebrates, nicotinic receptors are broadly classified into two subtypes based on their primary sites of expression: muscle-type nicotinic receptors and neuronal-type nicotinic receptors. (wikipedia.org)
  • The nicotinic acetylcholine receptor protein contains a binding site(s) for the neurotransmitter ACh and an intrinsic cationic channel specific for Na + , K + and Ca 2+ ions (in some brain subtypes) together with the physical mechanism that links the binding of ACh to the opening of the ion channel. (scholarpedia.org)
  • Electrical recordings from these muscles indicate that two distinct nicotinic receptor subtypes mediate excitation of the body muscles ( R ichmond and J orgensen 1999 ). (genetics.org)
  • Candidate gene association studies of the alpha 4 (CHRNA4) and beta 2 (CHRNB2) neuronal nicotinic acetylcholine receptor subunit genes in Alzheimer's disease. (antikoerper-online.de)
  • The muscle-type nicotinic receptor is a type of nicotinic acetylcholine receptor consisting of the subunit combination (α1)2β1δε (adult receptor) or (α1)2β1δγ (fetal receptor). (wikipedia.org)
  • They possess similarities with GABAA receptors, glycine receptors, and the type 3 serotonin receptors (which are all ionotropic receptors), or the signature Cys-loop proteins. (wikipedia.org)
  • Serotonin (5-hydroxytryptamine) type 3 receptors (5-HT 3 R) and nicotinic acetylcholine receptors are structurally and functionally related proteins, yet distinct members of the family of ligand-gated ion channels. (pnas.org)
  • To address this difficulty we have utilized the acetylcholine binding proteins (AChBPs) as surrogates of the receptor ligand binding domain (LBD). (une.edu)
  • QPRHHCARQRLR , corresponding to internal sequence amino acids 351-362 of Human Nicotinic Acetylcholine Receptor beta 2 (NP_000739.1). (abcam.com)
  • The muscarinic receptor and the nicotinic receptor are the two major types of cholinergic receptor, another name for an acetylcholine receptor. (wisegeek.com)
  • The actions of acetylcholine in the periphery are the result of activation of either inotropic nicotinic receptor or the metabotropic muscarinic receptor (Caufield and Birdsall, 1998). (thefreedictionary.com)
  • Based on these findings, the group at UNIFESP decided to test the hypothesis that stimulating the cholinergic system with a drug that binds to nicotinic receptors might attenuate inflammation in the lungs of mice that had not been genetically modified so as not to express VAChT. (eurekalert.org)
  • About 30 minutes before LPS injection, some of the mice were treated with PNU-282987, a compound that stimulates the alpha-7 nicotinic receptors. (eurekalert.org)
  • Zoli M, Léna C, Picciotto MR, Changeux JP (1998) Identification of four classes of brain nicotinic receptors using beta2 mutant mice. (springer.com)
  • 1997) Identification of nicotinic acetylcholine receptors on lymphocytes in the periphery as well as thymus in mice. (scirp.org)
  • Figure 1: Left: Schematic representation of the muscle-type nicotinic acetylcholine receptor, view from the synaptic cleft (upper view) and laterally (membrane represented in blue). (scholarpedia.org)
  • The assumption was that this channel was located in the part of the receptor that crosses the synaptic membrane, i.e. the transmembrane segments. (pasteur.fr)
  • This, again, could be envisioned to lead to three different assemblies because the two dimers in each receptor can be oriented in the clockwise, the counterclockwise, or both orientations when viewed from the synaptic cleft. (rupress.org)
  • According to Prado, studies suggest that acetylcholine has a protective effect on the lungs that is linked to activation of nicotinic receptors. (eurekalert.org)
  • The protein encoded by this gene is a nicotinic acetylcholine receptor subunit and a member of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. (nih.gov)
  • Benzocaine is a permanently uncharged species that inhibits the receptor by plugging the pore of the opened channel. (wikipedia.org)
  • A new study reports small fragments of the rabies virus binds to, and inhibits, nicotinic acetylcholine receptors in the brain, inducing frenzied behaviors. (neurosciencenews.com)
  • In honey bees, the neonicotinoid imidacloprid inhibits receptors for γ-aminobutyric acid (GABA), a major neurotransmitter in the central nervous system ( Thany, 2010 ). (biologists.org)
  • Each Nicotinic Acetylcholine Receptor beta 2 Antibody is fully covered by our Guarantee+, to give you complete peace of mind and the support when you need it. (novusbio.com)
  • Choose from our Nicotinic Acetylcholine Receptor beta 2 polyclonal antibodies and browse our Nicotinic Acetylcholine Receptor beta 2 monoclonal antibody catalog. (novusbio.com)
  • In normal physiological conditions, the receptor needs exactly two molecules of ACh to open. (wikipedia.org)
  • I'm also taking a course in neuroscience, and although they don't explicitly say it, their diagrams also suggest two Ach molecules binding to the receptor (in the attachment). (physicsforums.com)
  • What happens to molecules after binding to a taste receptor? (physicsforums.com)
  • Greater accumulation of beta amyloid "plaques" was accompanied by a reduction in neuronal nicotinic receptors - brain molecules crucial to memory function. (thefreedictionary.com)
  • Here we describe the egg-laying phenotypes of eight levamisole resistance genes, which affect the activity of levamisole-sensitive nicotinic receptors in nematodes. (genetics.org)
  • Seven of these genes, including the nicotinic receptor subunit genes unc-29, unc-38 , and lev-1 , were essential for the stimulation of egg laying by levamisole, though they had only subtle effects on egg-laying behavior in the absence of drug. (genetics.org)
  • Thus, these genes appear to encode components of a nicotinic receptor that can promote egg laying but is not necessary for egg-laying muscle contraction. (genetics.org)
  • MAFA controls autonomic nervous system-mediated insulin secretion by activating the transcription of nicotinic ( ChrnB2 and ChrnB4 ) receptor genes, which is impaired in patients with type 2 diabetes. (antikoerper-online.de)
  • Since nicotinic receptors help transmit outgoing signals for the sympathetic and parasympathetic systems, nicotinic receptor antagonists such as hexamethonium interfere with the transmission of these signals. (wikipedia.org)
  • Usually bound to by the neurotransmitter acetylcholine, activation of these excitatory receptors triggers the action potential in the cell, releases chemicals of reward and stimulates feelings of happiness. (biotechniques.com)
  • Nicotinic receptors are excitatory, ligand-gated channels that allow the movement of Na + , K + , and Ca 2+ ions across the cell membrane. (jneurosci.org)
  • At the resting membrane potential of a typical cortical neuron, the nicotinic current provides an excitatory or depolarizing influence, which is measured electrophysiologically in a voltage clamp as an inward current. (jneurosci.org)
  • Thus, for example, nicotinic receptor antagonists interfere with the baroreflex that normally corrects changes in blood pressure by sympathetic and parasympathetic stimulation of the heart. (wikipedia.org)
  • stimulation of these receptors causes muscular contraction. (bionity.com)
  • A new study, however, shows that pharmacological stimulation of a specific type of nicotinic receptor in cells of the immune system could be a strategy to treat inflammatory lung disease. (eurekalert.org)
  • Identify the key physiological effects that result from stimulation of nicotinic receptors by excessive amounts of acetylcholine. (cdc.gov)
  • In the peripheral nervous system: (1) they transmit outgoing signals from the presynaptic to the postsynaptic cells within the sympathetic and parasympathetic nervous system, and (2) they are the receptors found on skeletal muscle that receive acetylcholine released to signal for muscular contraction. (wikipedia.org)
  • Nicotinic antagonists that block the receptor include mecamylamine, dihydro-β-erythroidine, and hexamethonium. (wikipedia.org)
  • Morales A., Aleu J., Ivorra I., Ferragut J. A., González-Ros J. M., and Miledi R. (1995) Incorporation of reconstituted acetylcholine receptors from Torpedo into Xenopus oocyte membrane. (springer.com)
  • We present a refined model of the membrane-associated Torpedo acetylcholine (ACh) receptor at 4A resolution. (rcsb.org)
  • These were then confirmed by a host of researchers from around the world, in particular my eminent Japanese colleague, Shosaku Numa, who was the first to publish the entire Torpedo acetylcholine receptor sequence. (pasteur.fr)
  • Desensitization of the nicotinic acetylcholine (ACh) receptor of Torpedo electric organs was studied by monitoring activated [3H]perhydrohistrionicotoxin binding to the channel sites of the receptor. (aspetjournals.org)
  • Receptor desensitization was produced by incubating Torpedo membranes that had been pretreated with diisopropylfluorophosphate with ACh and was quenched by the addition of AChesterase. (aspetjournals.org)
  • Aside from the ACh that triggers nicotinic receptors, other types of neurotransmitters include serotonin , dopamine , and norepinephrine. (wisegeek.com)
  • thus nicotinic receptors may play a role in regulating serotonin response pathways in the egg-laying neuromusculature. (genetics.org)
  • The nicotinic acetylcholine receptor was the first membrane receptor of a neurotransmitter and ion channel that was characterized as a protein. (scholarpedia.org)
  • When the neurotransmitter, acetylcholine, attaches to the portion of the nicotinic receptor outside of the cell wall, it induces a conformational change that selectively opens up the channel to sodium ions. (cdc.gov)
  • In response to ligands, this receptor channel opens to conduct cations into the cell but desensitizes rapidly. (wingsforlife.com)
  • Provided herein are novel and selective high affinity .alpha.3.beta.4 nicotinic acetycholine receptor ligands and pharmaceutical compositions thereof. (patents.com)
  • Nicotinic receptors also fall under the category of an ionotropic receptor. (wisegeek.com)
  • An ionotropic receptor is a type of receptor that converts the ligand into an electrical signal. (wisegeek.com)
  • With their quick-fire means of function, ionotropic receptors are in contrast with metabotropic receptors. (wisegeek.com)
  • Nicotinic acetylcholine receptors are the best-studied of the ionotropic receptors. (wikipedia.org)
  • nicotinic acetylcholine receptor (AchR) from the rat brain. (sigmaaldrich.com)
  • Clones coding for the mouse nicotinic acetylcholine receptor (AChR) gamma subunit precursor have been selected from a cDNA library derived from a mouse myogenic cell line and sequenced. (caltech.edu)
  • Fong T. M. and McNamee M. G. (1986) Correlation between acetylcholine receptor function and structural properties of membranes. (springer.com)
  • The importance of the C-terminal region was further analysed by the use of chimeric nicotinic acid receptors, in which the C-terminal tail of HM74 and HM74A were exchanged. (gla.ac.uk)
  • 2012) . (D) Hypothetically, injection of a cRNA mixture of α4, α4 VFL , and β2 into oocytes could yield eight different receptors in the 3α:2β stoichiometry. (rupress.org)
  • In addition, since expression of functional unc-29 in muscle cells restored levamisole sensitivity under some but not all conditions, both neuronal and muscle cell UNC-29 receptors are likely to contribute to the regulation of egg-laying behavior. (genetics.org)
  • The HCAR2 gene is 96% homologous to HCAR3, but the HCAR3 receptor shares neither the specificity for NA, nor the range of functional effects. (bl.uk)
  • (D) The simplest way in which a dimeric β-6-α construct could lead to functional 3α:2β stoichiometry receptors is three sets of linked dimers assembling with a dangling β2 subunit. (rupress.org)
  • This result is consistent with the expression of the relatively rare α 5 nicotinic subunit in layer VI. (jneurosci.org)
  • In the past, recombinant expression of insect receptors has proved largely unsuccessful and in some (but not all) circumstances co‐expression with RIC‐3 has alleviated the problems. (bl.uk)
  • This hypothesis was tested by examining the regulation and desensitisation characteristics of each receptor in a heterologous expression system. (gla.ac.uk)
  • 2,6-Dimethylaniline (DMA), a molecule that mimics the hydrophobic moiety of lidocaine, has been found to bind the receptor at inter-subunit crevices of the trans-membrane spanning domain thereby causing non-competitive inhibition and restricting the channel from opening. (wikipedia.org)
  • Neuronal receptors showed a prolonged inhibition after exposure to low micromolar concentrations of mecamylamine. (aspetjournals.org)
  • Muscle-type receptors showed a transient inhibition by similar concentrations of mecamylamine, and NMDA receptors were only transiently inhibited by higher micromolar concentrations. (aspetjournals.org)
  • One example of a metabotropic receptor is the muscarinic acetylcholine receptor, a receptor charged with regulating the distribution of acetylcholine in the body, as well as other tasks within the body and brain . (wisegeek.com)
  • Researchers discovered that the rats most likely to self-administer addictive drugs had a particular receptor in the brain that is more responsive than the same receptor in rats least likely to self-administer addictive drugs. (nsf.gov)
  • Our experiments tested nicotinic excitation across postnatal development, using whole-cell recordings in prefrontal brain slices from rats. (jneurosci.org)
  • These receptors are widely distributed throughout the brain, and are highly expressed in addiction circuitry. (aspetjournals.org)
  • The study is being performed in order to learn more about AZD3480 (potential as treatment for patients with Alzheimer's Disease) and to investigate how much of AZD3480 is bound to the nicotinic receptors in the brain at different concentrations of AZD3480 in blood, as well as to investigate the period of time for this binding. (clinicaltrials.gov)
  • It links the brain with the immune system through effects of acetylcholine (ACh) particularly on the α7 nicotinic acetylcholine receptor (α7nAChR). (ersjournals.com)
  • Changes of learning and memory ability and brain nicotinic receptors of rat offspring with coal burning fluorosis. (fluoridealert.org)
  • In contrast, muscarinic acetylcholine receptors (mAChR) are prototypic G protein-coupled receptors. (intechopen.com)