文章基本信息

标题：Protective Effect of DY-9760e, a Calmodulin Antagonist, against Neuronal Cell Death
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作者：Hiromichi Takano ; Masunobu Sugimura ; Yoshito Kanazawa 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2004
卷号：27
期号：11
页码：1788-1791
DOI：10.1248/bpb.27.1788
出版社：The Pharmaceutical Society of Japan
摘要：An excessive elevation of intracellular Ca²⁺ levels is known to play a key role in the pathological events following cerebral ischemia. DY-9760e, 3-[2-[4-(3-chloro-2-methylphenylmethyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1 H -indazole dihydrochloride 3.5 hydrate, is a potent calmodulin antagonist that attenuates brain damage in focal ischemia models. In the present study, we investigated the effect of DY-9760e on neuronal cell death induced by a variety of cell-toxic stimuli that increase intracellular Ca²⁺. Cell death was induced by the exposure of primary cultured neurons to excitotoxic agents such as glutamate and N -methyl- D -aspartate, membrane-depolarizing agents such as veratridine and high KCl, or thapsigargin an endoplasmic reticulum Ca²⁺-ATPase inhibitor. Treatment with DY-9760e resulted in a dose-dependent prevention of neuronal cell death elicited by excitotoxicity, voltage-gated channel opening, and inhibition of endoplasmic reticulum Ca²⁺-ATPase. These results indicate that DY-9760e can rescue neurons from various types of cell-toxic stimuli, which may contribute to attenuation of brain injury after cerebral ischemia.
关键词：DY-9760e;calmodulin antagonist;neuronal cell death;intracellular Ca2+;cerebral ischemia