Some selective serotonin reuptake inhibitors inhibit dynamin I guanosine triphosphatase (GTPase)

Masahiro Otomo, Kiyofumi Takahashi, Hiroshi Miyoshi*, Kenichi Osada, Hideki Nakashima, Noboru Yamaguchi

*この研究の対応する著者

研究成果: Article査読

28 被引用数 (Scopus)

抄録

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 μM, 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.

本文言語English
ページ(範囲)1489-1495
ページ数7
ジャーナルBiological and Pharmaceutical Bulletin
31
8
DOI
出版ステータスPublished - 2008 8月
外部発表はい

ASJC Scopus subject areas

  • 分子医療
  • 薬理学、毒性学および薬学(全般)

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