Nakane H, Ooboshi H, Ibayashi S, Yao H, Sadoshima S, Fujishima M
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Neurosci Lett. 1995 Mar 31;188(3):151-4. doi: 10.1016/0304-3940(95)11417-u.
This study was designed to investigate the role of the L-type voltage sensitive calcium channel blocker, isradipine, in the ischemia-induced release of neurotransmitters. Male spontaneously hypertensive rats were subjected to cerebral ischemia for 60 min by bilateral carotid artery occlusion, and recirculated for 120 min. Isradipine (0.25 mg/kg n = 6) or vehicle (n = 6) was administered subcutaneously at 20 min before ischemia. In the striatum, cerebral blood flow was determined by the hydrogen clearance method and concentrations of extracellular dopamine and glutamate were measured by in vivo brain dialysis technique. Extracellular dopamine in the vehicle-treated group increased by 180-fold from the basal level, and glutamate by 24-fold during cerebral ischemia. Isradipine significantly attenuated the ischemic release of dopamine to 33-34% (P < 0.05) of the vehicle group, while it did not affect glutamate release. It is suggested that the release mechanism of dopamine and glutamate during cerebral ischemia may be different, especially in the dependence on the L-type calcium channels.
本研究旨在探讨L型电压敏感性钙通道阻滞剂伊拉地平在缺血诱导的神经递质释放中的作用。雄性自发性高血压大鼠通过双侧颈动脉闭塞进行60分钟的脑缺血，并再灌注120分钟。在缺血前20分钟皮下注射伊拉地平（0.25mg/kg，n = 6）或赋形剂（n = 6）。在纹状体中，通过氢清除法测定脑血流量，并通过体内脑透析技术测量细胞外多巴胺和谷氨酸的浓度。赋形剂处理组的细胞外多巴胺在脑缺血期间从基础水平增加了180倍，谷氨酸增加了24倍。伊拉地平显著将多巴胺的缺血性释放减弱至赋形剂组的33-34%（P < 0.05），而它不影响谷氨酸的释放。提示脑缺血期间多巴胺和谷氨酸的释放机制可能不同，尤其是在对L型钙通道的依赖性方面。
