线粒体K_(ATP)开放剂二氮嗪促进星形胶质细胞摄取谷氨酸  

Diazoxide increases glutamate uptake by astrocytes via activating mitochondrial ATP-sensitive potassium channels

作　　者：戴翠萍[1] 曾晓宁[1] 孙秀兰[1] 丁建花[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》2006年第4期398-401,共4页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金资助项目(№30572172);江苏省教育厅自然科学基金重点资助项目(№05KJA31014);江苏省卫生厅重大科研资助项目(№K200501)

摘　　要：目的:研究线粒体ATP敏感性钾通道(mito-chondrial ATP-sensitive potassium channel,mitoKATP)开放剂二氮嗪(diazoxide)对星形胶质细胞摄取谷氨酸(glutamate)的影响。方法:取新生大鼠脑星形胶质细胞作原代培养,用液体闪烁计数仪测定[3H]-D,L-谷氨酸的摄入量判断细胞的谷氨酸摄取功能。结果:二氮嗪呈浓度依赖性地促进星形胶质细胞摄取谷氨酸,且能抑制1-甲基-4-苯基吡啶离子(1-methyl-4-phenylpyridinium,MPP+)对星形胶质细胞摄取谷氨酸的损伤作用;浓度在100μmol.L-1以上时,二氮嗪可完全逆转MPP+对星形胶质细胞摄取谷氨酸的抑制作用;二氮嗪的上述作用可被选择性mito KATP阻断剂5-羟基癸酸(5-hydroxydecanoate,5-HD)拮抗。结论:二氮嗪通过开放mitoKATP增强星形胶质细胞谷氨酸转运体(glutamate transporters,GluTs)的功能。AIM： To demonstrate the effect of mitochondrial ATP-sensitive potassium channel opener, Diazoxide, on glutamate uptake activity of astrocyte. METHODS： Primary astrocytic cultures were prepared from cerebral cortices of rats within 3 days old. Glutamate uptake activity of astrocytes was measured using isotopic techniques to detect intracellular [^3H]-labeled D, L-glutamate concentration. RESULTS： Diazoxide increased [^3H]-glutamate uptake in a concentration-dependent manner, and could significantly reverse MPP^＋-induced glutamate uptake inhibition. The above effects of Diazoxide were blocked by 5-hydroxydecanoate, a selective mitochondrial ATP-sensitive potassium channel blocker. CONCLUSION： Diazoxide increase the activity of glutamate transporters in astrocytes by opening mitochondrial ATP-sensitive potassium channel.

关 键 词：线粒体ATP敏感性钾通道 二氮嗪 星形胶质细胞 谷氨酸转运体 

分 类 号：R338.2[医药卫生—人体生理学]