代谢型谷氨酸受体

代謝型麩胺酸受體被綠色螢光蛋白標記,顯現在螢光顯微鏡照片下的細胞當中[1]

代谢型谷氨酸受体(英語:metabotropic glutamate receptors,簡稱mGluR),屬於谷氨酸受体的一種類型(另一类为离子型谷氨酸受体),可藉由間接代謝過程進行活化。該受體是GPCR家族C組的成員[2]。就像所有麩胺酸鹽受體,該受體會與谷氨酸結合,是一種具有興奮性神經傳遞物質胺基酸

功能与结构编辑

在中枢和周围神经系统中,mGluR执行许多种功能:比如涉及学习記憶焦慮以及疼痛的感知[3]。它们在海马体小脑[4]大脑皮质等其他组织及周围组织[5]神经突触的突触前和突触后神經元都有发现。

如同其它的代谢型受体,mGluRs也有一个七跨膜结构域跨过细胞膜[6],但不像离子型受体,mGluRs并没有离子通道的作用,而是通过生化级联反应英语biochemical cascade来使其它蛋白(如离子通道)变构[7],从而改变突触的兴奋性。比如神经传递英语neurotransmission的突触前抑制[8]和突触后反应的调节甚至诱导[2][5][6][9]

mGluRs的二聚化英语GPCR oligomer需要激动剂的信号介导。[10]

分类编辑

八种不同的mGluR(mGluR1到mGluR8,基因为GRM1-GRM8)由其结构和生理活性[3]可分为I-III三个类型[2][4][5][9]。mGluR还可以进一步分为亚型,如mGluR7a和mGluR7b

概览编辑

代謝型麩胺酸受體概览
受体 [11][12] 基因 机制[11] 功能 激动剂和激活剂 拮抗剂 突触分布
I型 mGluR1 GRM1英语GRM1 Gq英语Gq alpha subunit, ↑Na+,[5]K+,[5]谷氨酸[9]

突触为主[15]
mGluR5 GRM5英语GRM5 Gq英语Gq alpha subunit, ↑Na+,[5]K+,[5]谷氨酸[9]
II型 mGluR2 GRM2英语GRM2 Gi/G0英语GiG0 alpha subunits

突触为主[15]
mGluR3 GRM3英语GRM3 Gi/G0英语GiG0 alpha subunits
III型 mGluR4 GRM4英语GRM4 Gi/G0英语GiG0 alpha subunits

突触为主[15]
mGluR6 GRM6英语GRM6 Gi/G0英语GiG0 alpha subunits
mGluR7 GRM7英语GRM7 Gi/G0英语GiG0 alpha subunits
mGluR8 GRM8英语GRM8 Gi/G0英语GiG0 alpha subunits

參考文獻编辑

  1. ^ Kammermeier PJ. Surface clustering of metabotropic glutamate receptor 1 induced by long Homer proteins. BMC Neurosci. 2006, 7: 1. PMC 1361788. PMID 16393337. doi:10.1186/1471-2202-7-1. 
  2. ^ 2.0 2.1 2.2 Bonsi P, Cuomo D, De Persis C, Centonze D, Bernardi G, Calabresi P, Pisani A. Modulatory action of metabotropic glutamate receptor (mGluR) 5 on mGluR1 function in striatal cholinergic interneurons. Neuropharmacology. 49. 2005,. Suppl 1: 104–13. PMID 16005029. doi:10.1016/j.neuropharm.2005.05.012. 
  3. ^ 3.0 3.1 Ohashi H, Maruyama T, Higashi-Matsumoto H, Nomoto T, Nishimura S, Takeuchi Y. A novel binding assay for metabotropic glutamate receptors using [3H] L-quisqualic acid and recombinant receptors (subscription required). Z. Naturforsch., C, J. Biosci. 2002, 57 (3-4): 348–55. PMID 12064739. 
  4. ^ 4.0 4.1 Hinoi E, Ogita K, Takeuchi Y, Ohashi H, Maruyama T, Yoneda Y. Characterization with [3H]quisqualate of group I metabotropic glutamate receptor subtype in rat central and peripheral excitable tissues. Neurochem. Int. 2001, 38 (3): 277–85. PMID 11099787. doi:10.1016/S0197-0186(00)00075-9. 
  5. ^ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 Chu Z, Hablitz JJ. Quisqualate induces an inward current via mGluR activation in neocortical pyramidal neurons. Brain Res. 2000, 879 (1-2): 88–92. PMID 11011009. doi:10.1016/S0006-8993(00)02752-9. 
  6. ^ 6.0 6.1 Platt SR. The role of glutamate in central nervous system health and disease--a review. Vet. J. 2007, 173 (2): 278–86. PMID 16376594. doi:10.1016/j.tvjl.2005.11.007. 
  7. ^ Gabriel L, Lvov A, Orthodoxou D, Rittenhouse A, Kobertz W, Melikian H. The Acid-sensitive, Anesthetic-activated Potassium Leak Channel, KCNK3, Is Regulated by 14-3-3β-dependent, Protein Kinase C (PKC)-mediated Endocytic Trafficking. JBC. 2012, 287 (39): 32354–32366. PMID 22846993. doi:10.1074/jbc.M112.391458. 
  8. ^ Sladeczek F., Momiyama A.,Takahashi T. (1992). "Presynaptic inhibitory action of metabotropic glutamate receptor agonist on excitatory transmission in visual cortical neurons". Proc. Roy. Soc. Lond. B 1993 253, 297-303.
  9. ^ 9.0 9.1 9.2 9.3 Endoh T. Characterization of modulatory effects of postsynaptic metabotropic glutamate receptors on calcium currents in rat nucleus tractus solitarius. Brain Res. 2004, 1024 (1-2): 212–24. PMID 15451384. doi:10.1016/j.brainres.2004.07.074. 
  10. ^ El Moustaine D, Granier S, Doumazane E; 等. Distinct roles of metabotropic glutamate receptor dimerization in agonist activation and G-protein coupling. Proc. Natl. Acad. Sci. U.S.A. 2012, 109 (40): 16342–7. PMC 3479612. PMID 22988116. doi:10.1073/pnas.1205838109. 
  11. ^ 11.0 11.1 If not otherwise specified in table:TABLE 1 Classification of the metabotropic glutamate (mGlu) receptors From the following article:
  12. ^ Swanson CJ, Bures M, Johnson MP, Linden AM, Monn JA, Schoepp DD. Metabotropic glutamate receptors as novel targets for anxiety and stress disorders. Nature Reviews Drug Discovery. 2005, 4 (2): 131–44. PMID 15665858. doi:10.1038/nrd1630. 
  13. ^ Skeberdis VA, Lan J, Opitz T, Zheng X, Bennett MV, Zukin RS. mGluR1-mediated potentiation of NMDA receptors involves a rise in intracellular calcium and activation of protein kinase C. Neuropharmacology. 2001, 40 (7): 856–65. PMID 11378156. doi:10.1016/S0028-3908(01)00005-3. 
  14. ^ Lea PM, Custer SJ, Vicini S, Faden AI. Neuronal and glial mGluR5 modulation prevents stretch-induced enhancement of NMDA receptor current. Pharmacol. Biochem. Behav. 2002, 73 (2): 287–98. PMID 12117582. doi:10.1016/S0091-3057(02)00825-0. 
  15. ^ 15.0 15.1 15.2 Shigemoto R, Kinoshita A, Wada E, Nomura S, Ohishi H, Takada M, Flor PJ, Neki A, Abe T, Nakanishi S, Mizuno N. Differential presynaptic localization of metabotropic glutamate receptor subtypes in the rat hippocampus (abstract). J. Neurosci. 1997, 17 (19): 7503–22. PMID 9295396. 
  16. ^ 16.0 16.1 Ambrosini A, Bresciani L, Fracchia S, Brunello N, Racagni G. Metabotropic glutamate receptors negatively coupled to adenylate cyclase inhibit N-methyl-D-aspartate receptor activity and prevent neurotoxicity in mesencephalic neurons in vitro (abstract). Mol. Pharmacol. 1995, 47 (5): 1057–64. PMID 7746273. 

外部链接编辑