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ська 中文 edit links article talk english read edit view history tools tools move to sidebar hide actions read edit view history general what links here related changes upload file permanent link page information cite this page get shortened url switch to legacy parser print export download as pdf printable version in other projects wikimedia commons wikidata item appearance move to sidebar hide from wikipedia the free encyclopedia widely distributed inhibitory receptor in the central nervous system glycine the glycine receptor abbreviated as glyr or glr is the receptor of the amino acid neurotransmitter glycine glyr is an ionotropic receptor that produces its effects through chloride currents it is one of the most widely distributed inhibitory receptors in the central nervous system and has important roles in a variety of physiological processes especially in mediating inhibitory neurotransmission in the spinal cord and brainstem 1 the receptor can be activated by a range of simple amino acids including glycine β alanine and taurine and can be selectively blocked by the high affinity competitive antagonist strychnine 2 caffeine is a competitive antagonist of glyr 3 cannabinoids enhance the function 4 the protein gephyrin has been shown to be necessary for glyr clustering at inhibitory synapses 5 6 glyr is known to colocalize with the gaba a receptor on some hippocampal neurons 5 nevertheless some exceptions can occur in the central nervous system where the glyr α1 subunit and gephyrin its anchoring protein are not found in dorsal root ganglion neurons despite the presence of gaba a receptors 7 history edit glycine and its receptor were first suggested to play a role in inhibition of cells in 1965 8 two years later experiments showed that glycine had a hyperpolarizing effect on spinal motor neurons 9 due to increased chloride conductance through the receptor 10 then in 1971 glycine was found to be localized in the spinal cord using autoradiography 11 all of these discoveries resulted in the conclusion that glycine is a primary inhibitory neurotransmitter of the spinal cord that works via its receptor arrangement of subunits edit a shows three agonists and one antagonist of the glycine receptor b the fetal form of the receptor is made up of five α2 subunits while the adult form is made up of both α1 and β subunits strychnine sensitive glyrs are members of a family of ligand gated ion channels receptors of this family are arranged as five subunits surrounding a central pore with each subunit composed of four α helical transmembrane segments 12 there are presently four known isoforms of the ligand binding α subunit α 1 4 of glyr glra1 glra2 glra3 glra4 and a single β subunit glrb the adult form of the glyr is the heteromeric α 1 β receptor which is believed to have a stoichiometry proportion of three α 1 subunits and two β subunits 13 or four α 1 subunits and one β subunit 14 the embryo form on the other hand is made up of five α2 subunits 15 the α subunits are also able to form functional homopentamers in heterologous expression systems in african clawed frog oocytes or mammalian cell lines which are useful for studies of channel pharmacokinetics and pharmacodynamics 14 the β subunit is unable to form functional channels without α subunits but determines the synaptic localization of glyrs and the pharmacological profile of glycinergic currents 16 function edit adults edit in mature adults glycine is an inhibitory neurotransmitter found in the spinal cord and regions of the brain 15 as it binds to a glycine receptor a conformational change is induced and the channel created by the receptor opens 17 as the channel opens chloride ions are able to flow into the cell which results in hyperpolarization in addition to this hyperpolarization which decreases the likelihood of action potential propagation glycine is also responsible for decreasing the release of both inhibitory and excitatory neurotransmitters as it binds to its receptor 18 this is called the shunting effect and can be explained by ohm s law as the receptor is activated the membrane conductance is increased and the membrane resistance is decreased according to ohm s law as resistance decreases so does voltage a decreased postsynaptic voltage results in a decreased release of neurotransmitters 18 embryos edit in developing embryos glycine has the opposite effect as it does in adults it is an excitatory neurotransmitter 18 this is because chloride has a more positive equilibrium potential in early stages of life due to the high expression of nkcc1 this moves one sodium one potassium and two chloride ions into the cell resulting in a higher intracellular chloride concentration when glycine binds to its receptor the result is an efflux of chloride instead of an influx as it happens in mature adults the efflux of chloride causes the membrane potential to become more positive or depolarized as the cells mature the k cl cotransporter 2 kcc2 is expressed which moves potassium and chloride out of the cell decreasing the intracellular chloride concentration this allows the receptor to switch to an inhibitory mechanism as described above for adults 18 glycine receptors in diseases edit disruption of glyr surface expression or reduced ability of expressed glyrs to conduct chloride ions results in the rare neurological disorder hyperekplexia the disorder is characterized by an exaggerated response to unexpected stimuli which is followed by a temporary but complete muscular rigidity often resulting in an unprotected fall chronic injuries as a result of the falls are symptomatic of the disorder 1 a mutation in glra1 is responsible for some cases of stiff person syndrome 19 ligands edit agonists edit β alanine d alanine gelsemine glycine hypotaurine ivermectin 20 l alanine l proline l serine milacemide quisqualamine sarcosine taurine thc l theanine positive allosteric modulators edit ethanol toluene zonisamide antagonists edit bicuculline brucine caffeine levorphanol picrotoxin strychnine tutin quercetin tranexamic acid 21 references edit 1 2 lynch jw october 2004 molecular structure and function of the glycine receptor chloride channel physiological reviews 84 4 1051 95 doi 10 1152 physrev 00042 2003 pmid 15383648 rajendra s lynch jw schofield pr 1997 the glycine receptor pharmacology therapeutics 73 2 121 146 doi 10 1016 s0163 7258 96 00163 5 pmid 9131721 duan l yang j slaughter mm august 2009 caffeine inhibition of ionotropic glycine receptors the journal of physiology 587 pt 16 4063 75 doi 10 1113 jphysiol 2009 174797 pmc 2756438 pmid 19564396 xiong wei 2011 cannabinoid potentiation of glycine receptors contributes to cannabis induced analgesia nature chemical biology 7 5 296 303 doi 10 1038 nchembio 552 pmc 3388539 pmid 21460829 1 2 lévi s logan sm tovar kr craig am january 2004 gephyrin is critical for glycine receptor clustering but not for the formation of functional gabaergic synapses in hippocampal neurons the journal of neuroscience 24 1 207 17 doi 10 1523 jneurosci 1661 03 2004 pmc 6729579 pmid 14715953 feng g tintrup h kirsch j nichol mc kuhse j betz h sanes jr november 1998 dual requirement for gephyrin in glycine receptor clustering and molybdoenzyme activity science 282 5392 1321 4 bibcode 1998sci 282 1321f doi 10 1126 science 282 5392 1321 pmid 9812897 lorenzo le godin ag wang f st louis m carbonetto s wiseman pw et al june 2014 gephyrin clusters are absent from small diameter primary afferent terminals despite the presence of gaba a receptors the journal of neuroscience 34 24 8300 17 doi 10 1523 jneurosci 0159 14 2014 pmc 6608243 pmid 24920633 aprison m h werman r november 1965 the distribution of glycine in cat spinal cord and roots life sciences 4 21 2075 2083 doi 10 1016 0024 3205 65 90325 5 pmid 5866625 werman r davidoff r a aprison m h may 1967 is glycine a neurotransmitter inhibition of motoneurones by iontophoresis of glycine nature 214 5089 681 683 bibcode 1967natur 214 681w doi 10 1038 214681a0 issn 0028 0836 pmid 4292803 s2cid 4198837 werman r davidoff r a aprison m h january 1968 inhibitory of glycine on spinal neurons in the cat journal of neurophysiology 31 1 81 95 doi 10 1152 jn 1968 31 1 81 issn 0022 3077 pmid 4384497 hökfelt tomas ljungdahl åke september 1971 light and electron microscopic autoradiography on spinal cord slices after incubation with labeled glycine brain research 32 1 189 194 doi 10 1016 0006 8993 71 90163 6 pmid 4329648 miyazawa a fujiyoshi y unwin n june 2003 structure and gating mechanism of the acetylcholine receptor pore nature 423 6943 949 55 bibcode 2003natur 423 949m doi 10 1038 nature01748 pmid 12827192 s2cid 205209809 kuhse j laube b magalei d betz h december 1993 assembly of the inhibitory glycine receptor identification of amino acid sequence motifs governing subunit stoichiometry neuron 11 6 1049 56 doi 10 1016 0896 6273 93 90218 g pmid 8274276 s2cid 25411536 1 2 kuhse j betz h kirsch j june 1995 the inhibitory glycine receptor architecture synaptic localization and molecular pathology of a postsynaptic ion channel complex current opinion in neurobiology 5 3 318 23 doi 10 1016 0959 4388 95 80044 1 pmid 7580154 s2cid 42056647 1 2 rajendra sundran lynch joseph w schofield peter r january 1997 the glycine receptor pharmacology therapeutics 73 2 121 146 doi 10 1016 s0163 7258 96 00163 5 pmid 9131721 galaz p barra r figueroa h mariqueo t aug 2015 advances in the pharmacology of lgics auxiliary subunits pdf pharmacol res 101 101 65 73 doi 10 1016 j phrs 2015 07 026 pmid 26255765 breitinger hans georg becker cord michael 2002 the inhibitory glycine receptor simple views of a complicated channel chembiochem 3 11 1042 1052 doi 10 1002 1439 7633 20021104 3 11 1042 aid cbic1042 3 0 co 2 7 issn 1439 7633 pmid 12404628 s2cid 41022948 1 2 3 4 xu tian le gong neng august 2010 glycine and glycine receptor signaling in hippocampal neurons diversity function and regulation progress in neurobiology 91 4 349 361 doi 10 1016 j pneurobio 2010 04 008 pmid 20438799 s2cid 247871 online mendelian inheritance in man omim stiff person syndrome sps 184850 shan q haddrill jl lynch jw april 2001 ivermectin an unconventional agonist of the glycine receptor chloride channel the journal of biological chemistry 276 16 12556 64 doi 10 1074 jbc m011264200 pmid 11278873 lecker i wang d s romaschin a d peterson m mazer c d orser b a 2012 tranexamic acid concentrations associated with human seizures inhibit glycine receptors the journal of clinical investigation 122 12 4654 4666 doi 10 1172 jci63375 pmc 3533541 pmid 23187124 external links edit glycine receptors at the u s national library of medicine medical subject headings mesh v t e ion channel cell surface receptor ligand gated ion channels cys loop receptor 5 ht serotonin 5 ht 3 a b c d e gaba gaba a α 1 α 2 α 3 α 4 α 5 α 6 β 1 β 2 β 3 γ 1 γ 2 γ 3 δ ε π θ gaba a ρ ρ 1 ρ 2 ρ 3 glycine α 1 α 2 α 3 α 4 β nicotinic acetylcholine monomers α1 α2 α3 α4 α5 α6 α7 α9 α10 β1 β2 β3 β4 δ ε pentamers α3 2 β4 3 α4 2 β2 3 α7 5 α1 2 β4 3 ganglion type α1 2 β1δε muscle type zinc zinc activated ionotropic glutamates ligand gated only ampa 1 2 3 4 kainate 1 2 3 4 5 voltage and ligand gated nmda 1 2a 2b 2c 2d 3a 3b l1a l1b orphan glud δ 1 δ 2 atp gated channels purinergic receptors p2x 1 2 3 4 5 6 7 v t e glycine receptor modulators receptor ligands glyr tooltip glycine receptor agonists β alanine β aba baba β aiba caesium d alanine d serine gaba glycine hypotaurine ivermectin l alanine l proline l serine l threonine mdl 27531 milacemide picolinic acid propofol quisqualamine sarcosine taurine positive modulators alcohols e g brometone chlorobutanol chloretone ethanol alcohol tert butanol 2m2p tribromoethanol trichloroethanol trifluoroethanol alkylbenzene sulfonate anandamide barbiturates e g pentobarbital sodium thiopental chlormethiazole d12 116 dihydropyridines e g nicardipine etomidate ginseng constituents e g ginsenosides e g ginsenoside rf glutamic acid glutamate ivermectin ketamine neuroactive steroids e g alfaxolone pregnenolone eltanolone pregnenolone acetate minaxolone org 20599 nitrous oxide penicillin g propofol tamoxifen tetrahydrocannabinol triclofos tropeines e g atropine bemesetron cocaine ly 278584 tropisetron zatosetron volatiles gases e g chloral hydrate chloroform desflurane diethyl ether ether enflurane halothane isoflurane methoxyflurane sevoflurane toluene trichloroethane methyl chloroform trichloroethylene xenon zinc antagonists 2 aminostrychnine 2 nitrostrychnine 4 phenyl 4 formyl n methylpiperidine αembtl bicuculline brucine cacotheline caffeine colchicine colubrine cyanotriphenylborate dendrobine diaboline endocannabinoids e g 2 ag anandamide aea gaboxadol thip gelsemine iso thaz isobutyric acid isonipecotic acid isostrychnine laudanosine n methylbicuculline n methylstrychnine n n dimethylmuscimol nipecotic acid pitrazepin pseudostrychnine quinolines e g 4 hydroxyquinoline 4 hydroxyquinoline 3 carboxylic acid 5 7 ciqa 7 ciq 7 tfq 7 tfqa ru 5135 sinomenine strychnine thaz thiocolchicoside tutin negative modulators amiloride benzodiazepines e g bromazepam clonazepam diazepam flunitrazepam flurazepam corymine cyanotriphenylborate daidzein dihydropyridines e g nicardipine nifedipine nitrendipine furosemide genistein ginkgo constituents e g bilobalide ginkgolides e g ginkgolide a ginkgolide b ginkgolide c ginkgolide j ginkgolide m imipramine nbqx neuroactive steroids e g 3α androsterone sulfate 3β androsterone sulfate deoxycorticosterone dhea sulfate pregnenolone sulfate progesterone opioids e g codeine dextromethorphan dextrorphan levomethadone levorphanol morphine oripavine pethidine thebaine picrotoxin i e picrotin and picrotoxinin pmba riluzole tropeines e g bemesetron ly 278584 tropisetron zatosetron verapamil zinc nmdar tooltip n methyl d aspartate receptor see here instead transporter blockers glyt1 tooltip sodium and chloride dependent glycine transporter 1 acppb alx 5407 nfps asp2535 bitopertin rg1678 ro4917838 cp 802079 ethanol alcohol glycyldodecylamide gsk1018921 iclepertin ly 2365109 mardepodect org 24598 org 25935 sch 900435 pesampator biib 104 pf 04958242 pf 03463275 sarcosine sng 12 synapsinae ssr 103 800 ssr 504 734 tilapertin glyt2 tooltip glycine transporter 2 alx 1393 amoxapine ethanol alcohol nagly opiranserin vvz 149 org 25543 vvz 368 see also receptor signaling modulators gaba receptor modulators gaba a receptor positive modulators ionotropic glutamate receptor modulators retrieved from https en wikipedia org w index php title glycine_receptor oldid 1378371600 categories glycine receptors membrane channels hidden categories articles with short description short description is different from wikidata this page was last edited on 4 october 2026 at 04 36 utc page was rendered with parsoid text is available under the creative commons attribution sharealike 4 0 license additional terms may apply by using this site you agree to the terms of use 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