Ⅱ、Ⅲ组亲代谢型谷氨酸受体激动剂逆转1-甲基-4-苯基吡啶离子抑制星形胶质细胞摄取谷氨酸

中国临床药理学与治疗学 ›› 2004, Vol. 9 ›› Issue (5): 485-489.

Ⅱ、Ⅲ组亲代谢型谷氨酸受体激动剂逆转1-甲基-4-苯基吡啶离子抑制星形胶质细胞摄取谷氨酸

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:2004-01-08 修回日期:2004-03-15 发布日期:2020-11-22
通讯作者: 胡刚, 男, 博士, 教授, 博士生导师, 中国药理学会理事, 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-mai l:ghu @njmu.edu.cn
作者简介:王芳, 女, 硕士研究生。
基金资助:
国家自然科学基金项目(No39970846); 江苏省卫生自然科学基金项目(NoH9922)

Group Ⅱ and Ⅲ metabotropic glutamate receptors agonists reverse 1-methyl-4-phenylpyridinium-induced glutamate uptake inhibition

WANG Fang, YAO Hong-Hong, HU Gang

Department of Pharmacology &Neurobiology, Nanjing Medical University, Nanjing 210029, Jiangsu, China

Received:2004-01-08 Revised:2004-03-15 Published:2020-11-22

摘要/Abstract

摘要： 目的探讨Ⅱ、Ⅲ 组亲代谢型谷氨酸受体(metabotropic glutamate receptors, mGluRs) 激动剂对1-甲基-4-苯基吡啶离子(1-methyl-4-phenylpyridinium,MPP⁺) 抑制星形胶质细胞摄取谷氨酸(Glu) 的影响。方法应用同位素标记法测定星形胶质细胞对培养液中[3H]-D, L-谷氨酸的摄取, 应用四氮唑(MTT) 比色法检测星形胶质细胞的活性。结果 MPP⁺150、200 μmol·L^-1可以明显抑制星形胶质细胞摄取Glu,抑制率达58.3 %和70.1 %, 但并不影响细胞活性;Ⅱ组mGluRs 激动剂(2S, 2' R, 3' R)-2-(2', 3'-dicarboxycyclopropyl) glycine (DCG-IV) 0.1、1、10,100 μmol·L^-1和Ⅲ组mGluRs 激动剂L(+)-2-amino-4-phosphonobutyric acid (L-AP4) 1、10、100 μmol·L^-1可以逆转MPP⁺对星形胶质细胞摄取Glu 的抑制作用。结论 MPP⁺抑制星形胶质细胞摄取Glu 可能与直接影响谷氨酸转运体(GluTs) 的功能有关, 激活星形胶质细胞上的Ⅱ、Ⅲ组mGluRs 可以通过促进GluTs 摄取Glu、进而降低细胞外液的Glu 浓度而发挥神经保护作用。

关键词: 亲代谢型谷氨酸受体, 1-甲基-4-苯基吡啶离子, 星形胶质细胞, 谷氨酸摄取

Abstract: AIM: To study the effects of group Ⅱ and Ⅲ metabotropic glutamate receptors (mGluRs) agonists on 1-methyl-4-phenylpyridinium (MPP +)-induced glutamate uptake inhibition. METHODS: The glutamate uptake into astrocytes was measured by using radio-ligand binding assay method, and the viability of astrocytes was investigated by MTT method. RESULTS: It was shown that MPP + (150, 200 μmol·L^-1) inhibited glutamate uptake into astrocytes, but produced no effect on the viability of astrocytes, and the inhibition rates were 58.3 % and 70.1 %, respectively.Group Ⅱ mGluRs agonist (2' S, 2' R, 3' R)-2-(2', 3'-dicarboxycyclopropyl) glycine (DCG-IV) (0.1, 1, 10, 100 μmol·L^-1) and Group Ⅲ mGluRs agonist L (+)-2-amino-4-phosphonobutyric acid (L-AP4) (1, 10, 100 μmol·L^-1) significantly reversed MPP +-induced glutamate uptake inhibition. CONCLUSION: MPP + directly inhibits the function of glutamate transporters, and group Ⅱ and Ⅲ mGluRs agonists produce neuroprotective effects by enhancing the activity of glutamate transporters.

Key words: metabotropic glutamate receptors, 1-methyl-4-phenylpyridinium, astrocytes, glutamate uptake

中图分类号:

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-苯基吡啶离子抑制星形胶质细胞摄取谷氨酸[J]. 中国临床药理学与治疗学, 2004, 9(5): 485-489.

WANG Fang, YAO Hong-Hong, HU Gang. Group Ⅱ and Ⅲ metabotropic glutamate receptors agonists reverse 1-methyl-4-phenylpyridinium-induced glutamate uptake inhibition[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(5): 485-489.

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