代謝型麩胺酸受體
外觀
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代謝型麩胺酸受體(英語:metabotropic glutamate receptors,簡稱mGluR),屬於麩胺酸受體的一種類型(另一類為離子型麩胺酸受體),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,該受體會與麩胺酸結合,是一種具有興奮性神經傳遞物質的胺基酸。
功能與結構
[編輯]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]。它們在腦的海馬迴、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。比如神經傳遞的突觸前抑制[8]和突觸後反應的調節甚至誘導[2][5][6][9]。
分類
[編輯]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
[編輯]受體 [11][12] | 基因 | 機制[11] | 功能 | 促效劑和活化劑 | 拮抗劑 | 突觸分布 | |
---|---|---|---|---|---|---|---|
I型 | mGluR1 | GRM1 | Gq, ↑Na+,[5] ↑K+,[5] ↓麩胺酸[9] |
|
|
突觸後為主[15] | |
mGluR5 | GRM5 | Gq, ↑Na+,[5] ↑K+,[5] ↓麩胺酸[9] | |||||
II型 | mGluR2 | GRM2 | Gi/G0 |
|
|
|
突觸前為主[15] |
mGluR3 | GRM3 | Gi/G0 | |||||
III型 | mGluR4 | GRM4 | Gi/G0 |
|
|
突觸前為主[15] | |
mGluR6 | GRM6 | Gi/G0 | |||||
mGluR7 | GRM7 | Gi/G0 | |||||
mGluR8 | GRM8 | Gi/G0 |
參考文獻
[編輯]- ^ 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).
- ^ 2.0 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.
- ^ 3.0 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).
- ^ 4.0 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.
- ^ 5.0 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.
- ^ 6.0 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.
- ^ 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.
- ^ 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.
- ^ 9.0 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.
- ^ 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.
- ^ 11.0 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:
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 15.0 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).
- ^ 16.0 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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