文章基本信息

标题：Some Selective Serotonin Reuptake Inhibitors Inhibit Dynamin I Guanosine Triphosphatase (GTPase)
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作者：Masahiro Otomo ; Kiyofumi Takahashi ; Hiroshi Miyoshi 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：2008
卷号：31
期号：8
页码：1489-1495
DOI：10.1248/bpb.31.1489
出版社：The Pharmaceutical Society of Japan
摘要：Neuronal dynamin I plays a critical role in the recycling of synaptic vesicles, and thus in nervous system function. We expressed and purified dynamin I to explore potentially clinically useful endocytosis inhibitors and to examine the mechanism of their action. We estimated the IC₅₀ of nineteen psychotropic drugs for dynamin I. The IC₅₀ values of two selective serotonin reuptake inhibitors (sertraline and fluvoxamine) were 7.3±1.0 and 14.7±1.6 μ M , respectively. Kinetic analyses revealed that fluvoxamine is a noncompetitive inhibitor of dynamin I guanosine triphosphatase (GTPase) with respect to guanosine 5′-triphosphate (GTP) and a competitive inhibitor with respect to L -phosphatidylserine (PS). Fluvoxamine may compete with PS for binding to the pleckstrin homology domain of dynamin I. On the other hand, sertraline was a mixed type inhibitor with respect to both GTP and PS. Our results indicate that sertraline and fluvoxamine may regulate the transportation of neurotransmitters by modulating synaptic vesicle endocytosis via the inhibition of dynamin I GTPase.
关键词：dynamin;guanosine triphosphatase;endocytosis;inhibitor;selective serotonin reuptake inhibitor