代谢型谷氨酸受体第5亚型的研究进展
作者：秦丽华 于恩华 徐群渊
单位：北京医科大学解剖学系 北京 100083
关键词：
解剖科学进展000203摘 要：代谢型谷氨酸受体第5亚型(mGluR5)高表达区域是纹状体、海马及大脑皮质。它是与G蛋白耦联的受体，通过1、4、5-三磷酸肌醇(1P3)和Ga2+作为第二信使系统发挥生物学效应。它与中枢神经系统发育的可塑性有关；可加强大脑皮质γ-氨基丁酸(GABA)能神经元的抑制性突触传递。在纹状体内，它可加强NM-DA受体的神经毒性作用，并与底丘脑核及多巴胺(DA)系统发生联系，可能参与调节基底节的运动，并可能与帕金森病(PD)动物模型中锥体外系症状的产生有关。在海马内，mGluR5可形成长时程增强效应(LTP)，与学习和记忆有关。
参考文献：
, 百拇医药 [1]Hollman M, Heinemann S. Coined glutamate receptors. A Rev Neurosci, 1994, 17(1): 31
[2]庞志平，徐天乐，吕国蔚.代射型谷氨酸受体的药理学和生理功能.神经解剖学杂志，1997，13(1)：87
[3]Houamed KM, Kuijper JL, Gilbert TL, et al. Cloning, expression, and gene structure of a G-protein-coupled glutamate receptor from rat brain. Science, 1991, 252(5010): 1318
[4]Tanabe Y, Masu M, Ishii T, et al. A family of metabotropic glutamate receptors. Neuron, 1992, 8(1): 169
, 百拇医药
[5]Abe T, Sugihara H, Nawa H, et al. Molecular characterization of a novel metabotropic glutamate receptor mGluR5 coupled to inositol phosphate/Ca2+ signal transduction. J Biol Chem,1992, 267(19): 13361
[6]Okamoto N, Hori S, Akazawa C,et al. Molecular characterization of a new metabotropic glutamate receptor mGluR7 coupled to inhibitory cyclic AMP signal transduction J. Biol Chem,1994, 269(2): 1231
[7]Saugstad JA, Kinzie JM, Shinohara MM, et al. Cloning and expression of rat metabotrpic glutamte receptor 8 reveals a distict pharamaeological profile. Molecular pharmacology, 1997,51(1): 119
, 百拇医药
[8]Pin J-P, Duvoisin R. The metabotropic glutamate receptors,structure and functions. Neuropharmacol, 1995, 34(1): 1
[9]Minakami R, Iida K, Hirakawa N, et al. The expression of two splice variants of metabotropic glutamate receptor subtype 5 in the rat brain and neuronal cells during development. J Neurochem, 1995, 65(4):1536
[10]Joly C, Gomeza J, Brabet I, et al. Molecular, functional, and pharmacological characterization of the metabotropic glutamate receptor type 5 splice variants, comparison with mGluR1. J Neurosci, 1995, 15(5pt 2): 3970
, 百拇医药
[11]Minakami R, Katsuki F, Sugiyama H. A variant of metabotropic glutamate receptor type 5: an evolutionally conserved insertion with no termination codon. Biochem Biophys Res Commun, 1993, 194(2): 622
[12]Test CM, Standaert DG, Young AB, et al. Metabotropic glutamate receptor mRNA expression in the basal ganglia of the rat. J Neurosci, 1994, 14(5): 3005
[13]Tanabe Y, Nomura A, Masu M, et al. Signal transduction,pharmacological properties, and expression patterns of two rat metabotropic glutamate receptors, mGluR3 and mGluR4. J Neurosci, 1993, 13(4): 1372
, http://www.100md.com
[14]王智明，李云庆，施际武.大鼠脑内代谢型谷氨酸受体5型(mG luR 5 )定位分布的免疫细胞化学研究.中国组织化学与细胞化学杂志，1996， 5(2)：131
[15]Daggett LP, Sacaan AI, Akong, et al. Molecular and functional characterization of recombinant human metabotropic glutamate receptor subtype 5. Neuropharmacology, 1995, 34 (8):871
[16]Ncgyessy L, Vidnyanszky Z, Kuhn R, et al. Light and electron microscopic demonstration of mGluR5 metabotropic glutamate receptor immunoreactive neuronal elements in the rat cerebellar cortex. J Comp Ncurol, 1997, 385(4): 641
, 百拇医药
[17]Shigemoto R, Kinoshita A, Wada E, et al. Differential presynaptic localization of metabotropic glutamate receptor subtypes in the rat hippocampus. J Neurosci, 1997, 17(19): 7503
[18]Romano C, Sesma MA, .Mcdonald CT, et al. Distribution of metabotropic glutamate receptor mGluR5 immunoreactivity in rat brain. J Comp Neurol, 1995, 355(3): 455
[19]Shigemoto R, Nomura S, Ohishi H, et al. Immunohistoc-hemical localizaation of a metabotropic glutamate receptor, mGluRS, intherat brain. NcurosciLett, 1993, 163(1): 53
, 百拇医药
[20]Minakami R, Katsuki F, Yamamoto T, et al. Molecular cloning and the functional expression of two isoforms of human metabotropic glutamate receptor subtype 5. Biochem Biophys Res Commun, 1994, 199(3): 1136
[21]Lin FF, Varney M, Sacaan Al, et al. Cloning and stable expression of thc mGluRlb subtype of human metabotropic glutamate receptors and pharmacological comparison with the mGluRSa subtype. Neuropharmaeology, 1997, 36(7): 917
, 百拇医药
[22]Montoliu C, Llansola M, Cuearella C, et al. Activation of the metabotropic glutamate receptor mGluR5 prevents glutamate toxicity in primary cultures of cerebellar neurons. J Pharmacol Exp Ther, 1997, 28(2): 643
[23]吕宝璋.兴奋性氨苛酸受体的分子生物学.国外医学分子生物学分册，1992，14(5)：205
[24]Casabona G, Knopfel T, Kuhn, R, et al. Expression and coupling to polyphosphoinositide hydrolysis of group I metabotropic glutamate receptors in early postnatal and adult rat brain.Eur J Neurosci, 1997, 9(1): 12
, http://www.100md.com
[25]Romano C, Vanden Poi AV, 0' Malley KL. Enhanced early developmental expression of the metabotroplc glutamate receptor mGluR5 in rat brain: protein, mRNA splice variants, and regional distrlbution. J Comp Neurol, 1996, 367(3): 403
[26]Catania MV, Landwehrmeyer GB, Testa CM, et al. Metabotropic glutamate receptors are differentially regulated during development. Neuroscience, 1994, 61(3): 481
[27]Chu Z, Hablitz JJ. Activation of group I mGluRs increases spontaneous IPSC frequency in rat frontal cortex. J Neurophysiol, 1998, 80(2):621
, http://www.100md.com
[28]Zhou FM, Hablitz JJ. Metabotropic glutamate receptor enhancement of spontaneous IPSCs in neocortical interneurons. J Neurophysiol, 1997, 78(5): 2287
[29]Miller S, Romano C, Cotman CW. Growth factor upregulation of a phosphoinositide-coupled metabotropic glutamate receptor in cortical astrocytes. J Neurosci, 1995, 15(9): 6103
[30]Rosdahl D, Seitzberg DA, Christen:eh T, et al. Changes in mRNA for metabotropic glutamate, receptors after transient cerebral ischaemia. Neuroreport, 1994, 5(5): 593, 百拇医药
单位：北京医科大学解剖学系 北京 100083
关键词：
解剖科学进展000203摘 要：代谢型谷氨酸受体第5亚型(mGluR5)高表达区域是纹状体、海马及大脑皮质。它是与G蛋白耦联的受体，通过1、4、5-三磷酸肌醇(1P3)和Ga2+作为第二信使系统发挥生物学效应。它与中枢神经系统发育的可塑性有关；可加强大脑皮质γ-氨基丁酸(GABA)能神经元的抑制性突触传递。在纹状体内，它可加强NM-DA受体的神经毒性作用，并与底丘脑核及多巴胺(DA)系统发生联系，可能参与调节基底节的运动，并可能与帕金森病(PD)动物模型中锥体外系症状的产生有关。在海马内，mGluR5可形成长时程增强效应(LTP)，与学习和记忆有关。
参考文献：
, 百拇医药 [1]Hollman M, Heinemann S. Coined glutamate receptors. A Rev Neurosci, 1994, 17(1): 31
[2]庞志平，徐天乐，吕国蔚.代射型谷氨酸受体的药理学和生理功能.神经解剖学杂志，1997，13(1)：87
[3]Houamed KM, Kuijper JL, Gilbert TL, et al. Cloning, expression, and gene structure of a G-protein-coupled glutamate receptor from rat brain. Science, 1991, 252(5010): 1318
[4]Tanabe Y, Masu M, Ishii T, et al. A family of metabotropic glutamate receptors. Neuron, 1992, 8(1): 169
, 百拇医药
[5]Abe T, Sugihara H, Nawa H, et al. Molecular characterization of a novel metabotropic glutamate receptor mGluR5 coupled to inositol phosphate/Ca2+ signal transduction. J Biol Chem,1992, 267(19): 13361
[6]Okamoto N, Hori S, Akazawa C,et al. Molecular characterization of a new metabotropic glutamate receptor mGluR7 coupled to inhibitory cyclic AMP signal transduction J. Biol Chem,1994, 269(2): 1231
[7]Saugstad JA, Kinzie JM, Shinohara MM, et al. Cloning and expression of rat metabotrpic glutamte receptor 8 reveals a distict pharamaeological profile. Molecular pharmacology, 1997,51(1): 119
, 百拇医药
[8]Pin J-P, Duvoisin R. The metabotropic glutamate receptors,structure and functions. Neuropharmacol, 1995, 34(1): 1
[9]Minakami R, Iida K, Hirakawa N, et al. The expression of two splice variants of metabotropic glutamate receptor subtype 5 in the rat brain and neuronal cells during development. J Neurochem, 1995, 65(4):1536
[10]Joly C, Gomeza J, Brabet I, et al. Molecular, functional, and pharmacological characterization of the metabotropic glutamate receptor type 5 splice variants, comparison with mGluR1. J Neurosci, 1995, 15(5pt 2): 3970
, 百拇医药
[11]Minakami R, Katsuki F, Sugiyama H. A variant of metabotropic glutamate receptor type 5: an evolutionally conserved insertion with no termination codon. Biochem Biophys Res Commun, 1993, 194(2): 622
[12]Test CM, Standaert DG, Young AB, et al. Metabotropic glutamate receptor mRNA expression in the basal ganglia of the rat. J Neurosci, 1994, 14(5): 3005
[13]Tanabe Y, Nomura A, Masu M, et al. Signal transduction,pharmacological properties, and expression patterns of two rat metabotropic glutamate receptors, mGluR3 and mGluR4. J Neurosci, 1993, 13(4): 1372
, http://www.100md.com
[14]王智明，李云庆，施际武.大鼠脑内代谢型谷氨酸受体5型(mG luR 5 )定位分布的免疫细胞化学研究.中国组织化学与细胞化学杂志，1996， 5(2)：131
[15]Daggett LP, Sacaan AI, Akong, et al. Molecular and functional characterization of recombinant human metabotropic glutamate receptor subtype 5. Neuropharmacology, 1995, 34 (8):871
[16]Ncgyessy L, Vidnyanszky Z, Kuhn R, et al. Light and electron microscopic demonstration of mGluR5 metabotropic glutamate receptor immunoreactive neuronal elements in the rat cerebellar cortex. J Comp Ncurol, 1997, 385(4): 641
, 百拇医药
[17]Shigemoto R, Kinoshita A, Wada E, et al. Differential presynaptic localization of metabotropic glutamate receptor subtypes in the rat hippocampus. J Neurosci, 1997, 17(19): 7503
[18]Romano C, Sesma MA, .Mcdonald CT, et al. Distribution of metabotropic glutamate receptor mGluR5 immunoreactivity in rat brain. J Comp Neurol, 1995, 355(3): 455
[19]Shigemoto R, Nomura S, Ohishi H, et al. Immunohistoc-hemical localizaation of a metabotropic glutamate receptor, mGluRS, intherat brain. NcurosciLett, 1993, 163(1): 53
, 百拇医药
[20]Minakami R, Katsuki F, Yamamoto T, et al. Molecular cloning and the functional expression of two isoforms of human metabotropic glutamate receptor subtype 5. Biochem Biophys Res Commun, 1994, 199(3): 1136
[21]Lin FF, Varney M, Sacaan Al, et al. Cloning and stable expression of thc mGluRlb subtype of human metabotropic glutamate receptors and pharmacological comparison with the mGluRSa subtype. Neuropharmaeology, 1997, 36(7): 917
, 百拇医药
[22]Montoliu C, Llansola M, Cuearella C, et al. Activation of the metabotropic glutamate receptor mGluR5 prevents glutamate toxicity in primary cultures of cerebellar neurons. J Pharmacol Exp Ther, 1997, 28(2): 643
[23]吕宝璋.兴奋性氨苛酸受体的分子生物学.国外医学分子生物学分册，1992，14(5)：205
[24]Casabona G, Knopfel T, Kuhn, R, et al. Expression and coupling to polyphosphoinositide hydrolysis of group I metabotropic glutamate receptors in early postnatal and adult rat brain.Eur J Neurosci, 1997, 9(1): 12
, http://www.100md.com
[25]Romano C, Vanden Poi AV, 0' Malley KL. Enhanced early developmental expression of the metabotroplc glutamate receptor mGluR5 in rat brain: protein, mRNA splice variants, and regional distrlbution. J Comp Neurol, 1996, 367(3): 403
[26]Catania MV, Landwehrmeyer GB, Testa CM, et al. Metabotropic glutamate receptors are differentially regulated during development. Neuroscience, 1994, 61(3): 481
[27]Chu Z, Hablitz JJ. Activation of group I mGluRs increases spontaneous IPSC frequency in rat frontal cortex. J Neurophysiol, 1998, 80(2):621
, http://www.100md.com
[28]Zhou FM, Hablitz JJ. Metabotropic glutamate receptor enhancement of spontaneous IPSCs in neocortical interneurons. J Neurophysiol, 1997, 78(5): 2287
[29]Miller S, Romano C, Cotman CW. Growth factor upregulation of a phosphoinositide-coupled metabotropic glutamate receptor in cortical astrocytes. J Neurosci, 1995, 15(9): 6103
[30]Rosdahl D, Seitzberg DA, Christen:eh T, et al. Changes in mRNA for metabotropic glutamate, receptors after transient cerebral ischaemia. Neuroreport, 1994, 5(5): 593, 百拇医药