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  

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

作　　者：王芳[1] 姚红红[1] 胡刚[1] 

机构地区：[1]南京医科大学药理学与神经生物学系

出　　处：《中国临床药理学与治疗学》2004年第5期485-489,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金项目 (№ 3 9970 846);江苏省卫生自然科学基金项目 (№H992 2 )

摘　　要：目的 :探讨Ⅱ、Ⅲ组亲代谢型谷氨酸受体(metabotropicglutamatereceptors ,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 [3 H] 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+ 15 0、2 0 0 μmol·L-1可以明显抑制星形胶质细胞摄取Glu ,抑制率达 5 8.3%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’ dicar boxycyclopropyl)glycine (DCG IV ) 0 .1、 1、 10 ,10 0 μmol·L-1和Ⅲ组mGluRs激动剂L(+) 2 amino 4 phosphonobutyricacid (L AP4 ) 1、10、10 0 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。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.

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 

分 类 号：R971.5[医药卫生—药品] R965.2[医药卫生—药学]