| 词条 | Glycine receptor |
| 释义 |
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 current. 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] Gephyrin has been shown to be necessary for GlyR clustering at inhibitory synapses.[4][4] GlyR is known to colocalize with the GABAA 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 GABAA receptors.[6]Arrangement of subunitsStrychnine-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.[7] There are presently four known isoforms of the α-subunit (α1-4) of GlyR that are essential to bind ligands (GLRA1, GLRA2, GLRA3, GLRA4) and a single β-subunit (GLRB). The adult form of the GlyR is the heteromeric α1β receptor, which is believed to have a stoichiometry (proportion) of three α1 subunits and two β subunits [8] or four α1 subunits and one β subunit.[9] The α-subunits are also able to form functional homo-pentameric receptors in heterologous expression systems in African clawed frog's oocytes or mammalian cell lines,[9] and the α1 homomeric receptor is essential for studies of channel pharmacokinetics and pharmacodynamics.[10]Glycine receptors in diseasesDisruption 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.[11] LigandsAgonists
PAMs
Antagonists
References1. ^1 {{cite journal | vauthors = Lynch JW | title = Molecular structure and function of the glycine receptor chloride channel | journal = Physiological Reviews | volume = 84 | issue = 4 | pages = 1051–95 | date = October 2004 | pmid = 15383648 | doi = 10.1152/physrev.00042.2003 | citeseerx = 10.1.1.326.8827 }} 2. ^{{cite journal |doi=10.1016/S0163-7258(96)00163-5 |title=The glycine receptor |journal=Pharmacology & Therapeutics |volume=73 |issue=2 |pages=121–146 |year=1997 |last1=Rajendra |first1=Sundran |last2=Lynch |first2=Joseph W. |last3=Schofield |first3=Peter R. }} 3. ^{{cite journal | vauthors = Duan L, Yang J, Slaughter MM | title = Caffeine inhibition of ionotropic glycine receptors | journal = The Journal of Physiology | volume = 587 | issue = Pt 16 | pages = 4063–75 | date = August 2009 | pmid = 19564396 | pmc = 2756438 | doi = 10.1113/jphysiol.2009.174797 }} 4. ^{{cite journal |doi=10.1126/science.282.5392.1321 |title=Dual Requirement for Gephyrin in Glycine Receptor Clustering and Molybdoenzyme Activity |journal=Science |volume=282 |issue=5392 |pages=1321–1324 |year=1998 |last1=Feng |first1=G. }} 5. ^1 {{cite journal | vauthors = Lévi S, Logan SM, Tovar KR, Craig AM | title = Gephyrin is critical for glycine receptor clustering but not for the formation of functional GABAergic synapses in hippocampal neurons | journal = The Journal of Neuroscience | volume = 24 | issue = 1 | pages = 207–17 | date = January 2004 | pmid = 14715953 | doi = 10.1523/JNEUROSCI.1661-03.2004 }} 6. ^{{cite journal | vauthors = Lorenzo LE, Godin AG, Wang F, St-Louis M, Carbonetto S, Wiseman PW, Ribeiro-da-Silva A, De Koninck Y | title = Gephyrin clusters are absent from small diameter primary afferent terminals despite the presence of GABA(A) receptors | journal = The Journal of Neuroscience | volume = 34 | issue = 24 | pages = 8300–17 | date = June 2014 | pmid = 24920633 | doi = 10.1523/JNEUROSCI.0159-14.2014 }} 7. ^{{cite journal | vauthors = Miyazawa A, Fujiyoshi Y, Unwin N | title = Structure and gating mechanism of the acetylcholine receptor pore | journal = Nature | volume = 423 | issue = 6943 | pages = 949–55 | date = June 2003 | pmid = 12827192 | doi = 10.1038/nature01748 }} 8. ^{{cite journal | vauthors = Kuhse J, Laube B, Magalei D, Betz H | title = Assembly of the inhibitory glycine receptor: identification of amino acid sequence motifs governing subunit stoichiometry | journal = Neuron | volume = 11 | issue = 6 | pages = 1049–56 | date = December 1993 | pmid = 8274276 | doi = 10.1016/0896-6273(93)90218-G }} 9. ^1 {{cite journal | vauthors = Kuhse J, Betz H, Kirsch J | title = The inhibitory glycine receptor: architecture, synaptic localization and molecular pathology of a postsynaptic ion-channel complex | journal = Current Opinion in Neurobiology | volume = 5 | issue = 3 | pages = 318–23 | date = June 1995 | pmid = 7580154 | doi = 10.1016/0959-4388(95)80044-1 }} 10. ^{{cite journal | vauthors = Lewis TM, Schofield PR, McClellan AM | title = Kinetic determinants of agonist action at the recombinant human glycine receptor | journal = The Journal of Physiology | volume = 549 | issue = Pt 2 | pages = 361–74 | date = June 2003 | pmid = 12679369 | pmc = 2342959 | doi = 10.1113/jphysiol.2002.037796 }} 11. ^{{OMIM|184850|STIFF-PERSON SYNDROME; SPS}} 12. ^{{cite journal | vauthors = Shan Q, Haddrill JL, Lynch JW | title = Ivermectin, an unconventional agonist of the glycine receptor chloride channel | journal = The Journal of Biological Chemistry | volume = 276 | issue = 16 | pages = 12556–64 | date = April 2001 | pmid = 11278873 | doi = 10.1074/jbc.M011264200 }} External links
2 : Ionotropic receptors|Cell signaling |
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