代謝型麩胺酸受體

代謝型穀氨酸受體(英語:metabotropic glutamate receptors,簡稱mGluR),屬於穀氨酸受體的一種類型(另一類為離子型穀氨酸受體),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,該受體會與穀氨酸結合,是一種具有興奮性神經傳遞物質胺基酸

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]
麩胺酸

功能與結構

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在中樞和周圍神經系統中,mGluR執行許多種功能:比如涉及學習記憶焦慮以及疼痛的感知[3]。它們在海馬體小腦[4]大腦皮質等其他組織及周圍組織[5]神經突觸的突觸前和突觸後神經元都有發現。

如同其它的代謝型受體,mGluRs也有一個七跨膜結構域跨過細胞膜[6],但不像離子型受體,mGluRs並沒有離子通道的作用,而是通過生化級聯反應來使其它蛋白(如離子通道)變構[7],從而改變突觸的興奮性。比如神經傳遞英語neurotransmission的突觸前抑制[8]和突觸後反應的調節甚至誘導[2][5][6][9]

mGluRs的二聚化英語GPCR oligomer需要激動劑的信號介導。[10]

分類

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八種不同的mGluR(mGluR1到mGluR8,基因為GRM1-GRM8)由其結構和生理活性[3]可分為I-III三個類型[2][4][5][9]。mGluR還可以進一步分為亞型,如mGluR7a和mGluR7b

概覽

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代謝型麩胺酸受體概覽
受體 [11][12] 基因 機制[11] 功能 激動劑和激活劑 拮抗劑 突觸分布
I型 mGluR1 GRM1英語GRM1 Gq英語Gq alpha subunit, ↑Na+,[5]K+,[5]穀氨酸[9]

突觸為主[15]
mGluR5 GRM5英語GRM5 Gq英語Gq alpha subunit, ↑Na+,[5]K+,[5]穀氨酸[9]
II型 mGluR2 GRM2英語GRM2 Gi/G0英語GiG0 alpha subunits

突觸為主[15]
mGluR3 GRM3英語GRM3 Gi/G0英語GiG0 alpha subunits
III型 mGluR4 GRM4英語GRM4 Gi/G0英語GiG0 alpha subunits

突觸為主[15]
mGluR6 GRM6英語GRM6 Gi/G0英語GiG0 alpha subunits
mGluR7 GRM7英語GRM7 Gi/G0英語GiG0 alpha subunits
mGluR8 GRM8英語GRM8 Gi/G0英語GiG0 alpha subunits

參考文獻

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  1. ^ Kammermeier PJ. Surface clustering of metabotropic glutamate receptor 1 induced by long Homer proteins. BMC Neurosci. 2006, 7: 1 [2014-04-27]. PMC 1361788 . PMID 16393337. doi:10.1186/1471-2202-7-1. (原始內容存檔於2015-09-23). 
  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 [2014-04-28]. PMID 12064739. (原始內容存檔 (PDF)於2005-10-27). 
  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; et al. 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頁面存檔備份,存於網際網路檔案館) 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 [2014-04-28]. PMID 9295396. (原始內容存檔於2008-07-05). 
  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 [2014-04-28]. PMID 7746273. (原始內容存檔於2008-08-28). 

外部連結

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