title: Some selective serotonin reuptake inhibitors inhibit dynamin I guanosine triphosphatase (GTPase).
abstract: 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 IC(50) of nineteen psychotropic drugs for dynamin I. The IC(50) values of two selective serotonin reuptake inhibitors (sertraline and fluvoxamine) were 7.3+/-1.0 and 14.7+/-1.6 microM, 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.
authors.affiliation: Department of Neuropsychiatry, St. Marianna University School of Medicine, Kanagawa, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Otomo
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Takahashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyoshi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Osada
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakashima
authors.forename: Noboru
authors.initials: N
authors.lastname: Yamaguchi
mesh_terms: D000818:Animals; D034284:Dynamin I / Q000037:antagonists & inhibitors* / Q000235:genetics; D004705:Endocytosis / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004926:Escherichia coli / Q000235:genetics; D016666:Fluvoxamine / Q000494:pharmacology; D005822:Genetic Vectors; D007700:Kinetics; D051379:Mice; D010957:Plasmids / Q000235:genetics; D011619:Psychotropic Drugs / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline / Q000494:pharmacology
chemical_list: D034284:Dynamin I; D004791:Enzyme Inhibitors; D016666:Fluvoxamine; D011619:Psychotropic Drugs; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline