II,III组亲代谢型谷氨酸受体激动剂逆转1-甲基-4-苯基吡啶离子抑制C6胶质瘤细胞摄取谷氨酸

中国临床药理学与治疗学 ›› 2005, Vol. 10 ›› Issue (10): 1096-1099.

II,III组亲代谢型谷氨酸受体激动剂逆转1-甲基-4-苯基吡啶离子抑制C6胶质瘤细胞摄取谷氨酸

王芳, 姚红红, 胡刚

南京医科大学药理学与神经生物学系, 南京 210029, 江苏

收稿日期:2005-09-09 修回日期:2005-09-30 发布日期:2020-11-23
通讯作者: 胡刚,男,博士,教授,博士生导师,研究方向:神经退行性疾病的病因学与实验治疗学研究。Tel:025-86863108 E-mail:ghu@njmu.edu.cn
作者简介:王芳,女,硕士。
基金资助:
国家自然科学基金(No39970846);江苏省卫生自然科学基金(Noll9922)

Group I and III metabotropic glutamate receptors agonists reverse 1-methyl-4-phenylpyridinium-induced glutamate uptake inhibition in C6 glioma cells

WANG Fang, YAO Hong-hong, HU Gang

Department of Pharmacology & Neurobiology, Nanjing Medical Uniersity, Nanjing 210029, China

Received:2005-09-09 Revised:2005-09-30 Published:2020-11-23

摘要/Abstract

摘要： 目的: 探讨II、III组亲代谢型谷氨酸受体(metahotropic glutamate receptors,mGluRs)激动剂对1-甲基-4-苯基吡啶离子(1-metyl-4-phenylpyridihium,MPP⁺)抑制C6胶质瘤细胞摄取谷氨酸(glutamate,Glu)的影响。方法: 应用同位素标记法测定C6胶质瘤细胞对培养液中[³H]-D,L- 谷氨酸的摄取。结果: II组mGlu品激动剂(2S,2' R,3' R)-2-(2',3' -dicarboxycyclopropyl)glyC'ine (DCC-IV)和III组mGluRs激动剂L (+)-2-amino-4-phosphonobutyric acid (L-AP4) 100μmol·L-l可以逆转MPP⁺抑制C6胶质瘤细胞摄取Glu的作用,而II组mGluRs拮抗剂(RS)I-Amino-5-phosphonoinan^-1-carboxylic acid (APICA)和III组mGlu Rs拮抗剂(RS)-α-me出ylserine-0-phosphate(MSOP)可以完全阻断其激动剂的逆转作用。结论: 激活C6胶质瘤细胞上的II、III组mGluRs可以通过促进谷氨酸转运体摄取Glu、进而降低细胞外液的Clu浓度。

关键词: 亲代谢型谷氨酸受体, I-甲基-4苯基吡啶离子, C6胶质瘤细胞, 谷氨酸摄取

Abstract: AIM: To study the effect of group II and Ill metabotropic glutamate receptors (mGluRs) agonistson 1-methyl-4-phenylpyridinium (MPP⁺) induced gluta-mate uptake inhibition in C6 glioma cell.METHODS: The glutamate uptake into astrocytes was measured by using radio-ligand binding assay method.RESULTS: It was shown that Group II mGluRs agonist (2 ‘S, 2'R, 3'R)-2-(2 ‘ 3'-dicarboxycyclopropyl glycine (DCG-IV(100μmol·L^-1) and Group II mGluRs agonist L (+)-2amino-4-phosphonobutyric acid (L-AP4) (100μmol·L^-1) significantly reversed Mpp⁺-induced gluta-mate uptake inhibition. Furthermore, the enhancementeffects of DCG-IV and L-AP4 were blocked by their re-spective antagonists, (RS)^-1-Amino-5-phosphonoinan^-1carboxylic acid (APICA and (RS)-α-methylserine-Ophosphate (MSOP).CONCLUSION: Group II and Ill mGluRs agonists produce neuroprotective effects byenhancing the activity of glutamate transporters.

Key words: metabotropic glutamate receptors, MPP⁺, C6 glioma cells, glutamate uptake

中图分类号:

R730.1

王芳, 姚红红, 胡刚. II,III组亲代谢型谷氨酸受体激动剂逆转1-甲基-4-苯基吡啶离子抑制C6胶质瘤细胞摄取谷氨酸[J]. 中国临床药理学与治疗学, 2005, 10(10): 1096-1099.

WANG Fang, YAO Hong-hong, HU Gang. Group I and III metabotropic glutamate receptors agonists reverse 1-methyl-4-phenylpyridinium-induced glutamate uptake inhibition in C6 glioma cells[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2005, 10(10): 1096-1099.

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