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

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

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-metyl-4-phenylpyridinium，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mGluRs激动剂(2S，2’R，3’R)-2-(2’，3’-di-carboxycyclopropyl)glycine(DCG-Ⅳ)和Ⅲ组mGluRs激动刺L(+)-2-amino-4-phosphonobutyric acid(LAP4)100μmol·L^(-1)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)-1-Amino-5-phosphonoinan-1-carboxylic acid(APICA)和Ⅲ组mGluRs拮抗剂(RS)-α-methvlserine-O-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Glu浓度。

AIM： To study the effect of group Ⅱ and Ⅲ metabotropic glutamate receptors （mGluRs） agonists on 1-methyl-4-phenylpyridinium （MPP^＋ ）-induced glutamate uptake inhibition in C6 glioma cells. 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 Ⅲ mGluRs agonist L （ ＋ ）- 2-amino-4-phosphonobutyric acid （ L-AP4 ） （ 100 μmol·L^-1） significantly reversed MPP^＋ -induced glutamate uptake inhibition. Furthermore, the enhancement effects of DCG-Ⅳ and L-AP4 were blocked by their respective antagonists, （ RS）-1-Amino-5-phosphonoinan-1-carboxylic acid （ APICA ） and （ RS ）-α-methylserine-O-phosphate （MSOP）. CONCLUSION： Group Ⅱ and Ⅲ mGluRs agonists produce neuroprotective effects by enhancing the activity of glutamate transporters.