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

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。

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

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.