线粒体KATP开放剂二氮嗪促进星形胶质细胞摄取谷氨酸

中国临床药理学与治疗学 ›› 2006, Vol. 11 ›› Issue (4): 398-401.

线粒体K_ATP开放剂二氮嗪促进星形胶质细胞摄取谷氨酸

戴翠萍^1,2, 曾晓宁¹, 孙秀兰¹, 丁建花¹, 胡刚¹

¹南京医科大学药理学与神经生物学系, 南京210029, 江苏;
²淮阴卫生学校, 淮安223000, 江苏

收稿日期:2006-03-01 修回日期:2006-03-20 出版日期:2006-04-26 发布日期:2020-12-08
通讯作者: 胡刚, 男, 博士, 教授, 博士生导师, 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-mail:gh@njmu.edu.cn
作者简介:戴翠萍, 女, 讲师, 在读硕士研究生, 研究方向:神经药理。Tel:13861671961 　E-mail:hywxsmu@yahoo.com.cn
基金资助:
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)

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

DAI Cui-ping^1,2, ZENG Xiao-ning¹, SUN Xiu-lan¹, DING Jian-hua¹, HU Gang¹

¹Department of Pharmacology & Neurobiology, Nanjing Medical University, Nanjing 210029, Jiangsu, China;
²School of Huaiying Health, Huaian 223000, Jiangsu, China

Received:2006-03-01 Revised:2006-03-20 Online:2006-04-26 Published:2020-12-08

摘要/Abstract

摘要： 目的:研究线粒体ATP 敏感性钾通道(mitochondrial 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100 μmol·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。

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

Abstract: 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.

Key words: mitochondrial ATP-sensitive potassium channel, diazoxide, astrocyte, glutamate transporters

中图分类号:

R338.2

戴翠萍, 曾晓宁, 孙秀兰, 丁建花, 胡刚. 线粒体K_ATP开放剂二氮嗪促进星形胶质细胞摄取谷氨酸[J]. 中国临床药理学与治疗学, 2006, 11(4): 398-401.

DAI Cui-ping, ZENG Xiao-ning, SUN Xiu-lan, DING Jian-hua, HU Gang. Diazoxide increases glutamate uptake by astrocytes via activating mitochondrial ATP-sensitive potassium channels[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2006, 11(4): 398-401.

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