埃他卡林增强星形胶质细胞摄取谷氨酸的作用

目的研究新型ATP敏感性钾通道开放剂(KATPCO)埃他卡林(iptakalim,Ipt)对星形胶质细胞摄取谷氨酸的影响。方法取新生大鼠脑星形胶质细胞作原代培养，将Ipt直接作用于细胞，观察它对正常和6-羟基多巴胺(6-OHDA)损伤模型细胞摄取谷氨酸的影响；分别加入阳性对照药吡那地尔和非特异性钾通道阻断药格列本脲分析Ipt的作用机制。根据［³H］标记的D,L-谷氨酸摄入量判断细胞谷氨酸摄取作用强度。结果Ipt和吡那地尔都能增强星形胶质细胞的谷氨酸摄取作用、逆转6-OHDA引起的谷氨酸摄取抑制效应，预先加入格列本脲后，上述作用均被取消。结论埃他卡林可能通过促进钾通道开放增强星形胶质细胞摄取谷氨酸的作用。

Iptakalim enhances astrocytic glutamate uptake activity

AIM: To investigate the effect of iptakalim (Ipt), a novel ATP-sensitive potassium channel opener (KATPCO), on astrocyte glutamate uptake activity. The mechanism of action involved was also examined. METHODS: Primary cultures of astrocytes were prepared from cerebral cortexes of 1 to 2 days old Sprague-Dawley rats. Cultures were preincubated with iptakalim of various concentrations with the absence or presence of 6-hydroxydopamine (6-OHDA, 50 micromol x L(-1)). Then, the cells were treated with pinacidil (10 micromol x L(-1), K+ channel opener) instead of iptakalim and pretreated with glibenclamide (20 micromol x L(-1), ATP-sensitive K+ channel inhibitor) before pinacidil or iptakalim was added into the medium so that the mechanism of action of iptakalim could be analysed. Astrocyte glutamate uptake activity was determined by intracellular concentration of 3H labeled D,L-glutamate, using isotope techniques. RESULTS: Both iptakalim and pinacidil were shown to increase glutamate uptake activity of astrocytes and reverse inhibitory effect induced by 6-OHDA. But the increased and reversed effects of iptakalim or pinacidil on astrocytic glutamate uptake were found to be completely antagonized by glibenclamide. CONCLUSION: These data indicated that iptakalim can enhance astrocytic glutamate uptake activity due to its K+ channel opening properties and lessen glutamate excitotoxicity. Iptakalim may be useful for the therapy of Parkinson's disease.