盐酸埃他卡林对PD模型大鼠脑内突触体谷氨酸摄取的影响

Iptakalim hydrochloride enhances glutamate uptake activity in synaptosomes from rat models of Parkinsons disease

目的 研究谷氨酸转运体功能改变与帕金森病(Parkinson’sdisease ,PD)发病的相关性 ,探讨新型ATP敏感性钾通道 (ATPsensitivepotassiumchannel,KATP)开放剂盐酸埃他卡林 (Iptakalimhydrochloride ,Ipt)对PD模型大鼠脑内突触体摄取谷氨酸的影响及其机制。方法 采用 6 hydrox ydopamine(6 OHDA)建立PD大鼠模型 ,制备脑组织突触体 ;用同位素标记法测定L [3 H] glutamate摄取活性。 结果 PD模型大鼠纹状体和皮层的谷氨酸转运功能明显降低 ;Ipt(10、5 0和 10 0 μmol·L-1)具有恢复转运功能的作用 ,此作用可被KATP阻断剂Glibenclamide (2 0 μmol·L-1)逆转。结论 谷氨酸转运体功能下降与PD发病密切相关 ;Ipt通过激活KATP发挥促进谷氨酸摄取的作用 。

AIM To study the relationship between the activity of glutamate transporters and Parkinson's disease (PD), examine whether a novel ATP sensitive potassium (K ATP) channel opener Iptakalim (Ipt) hydrochloride enhances glutamate uptake activity, and to investigate its mechanisms. METHODS Rats were stereotaxically injected with 6 hydroxydopamine (6 OHDA) in SNpc. The synaptosomes from normal and PD rats were isolated, and [ 3H] glutamate uptake in synaptosomes was measured by using liquid scintillation counting. RESULTS [ 3H] glutamate uptake by synaptosomes from striatum and cerebral cortex of PD rats decreased and the redution was recovered by administration with Ipt (10, 50, 100 μmol·L -1 ). The protective effect of Ipt was blocked by co adiministration with glibenclamide (20 μmol·L -1 ), an inhibitor of sulphonylurea receptors. CONCLUSION Our results demonstrate for the first time the protective role of K ATP channel in glutamate uptake of synaptosomes and conceptually support the view that Ipt may have potential and feasibility in therapy for PD.