Some Selective Serotonin Reuptake Inhibitors Inhibit Dynamin I Guanosine Triphosphatase (GTPase)
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- Otomo Masahiro
- Department of Neuropsychiatry, St. Marianna University School of Medicine
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- Takahashi Kiyofumi
- Department of Neuropsychiatry, St. Marianna University School of Medicine
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- Miyoshi Hiroshi
- Department of Microbiology, St. Marianna University School of Medicine
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- Osada Kenichi
- Department of Neuropsychiatry, St. Marianna University School of Medicine
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- Nakashima Hideki
- Department of Microbiology, St. Marianna University School of Medicine
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- Yamaguchi Noboru
- Department of Neuropsychiatry, St. Marianna University School of Medicine
Bibliographic Information
- Other Title
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- Some selective serotonin reuptake inhibitors inhibit dynamin 1 guanosine triphosphatase (GTPase)
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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 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.
Journal
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- Biological and Pharmaceutical Bulletin
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Biological and Pharmaceutical Bulletin 31 (8), 1489-1495, 2008
The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390001204624808320
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- NII Article ID
- 110006839006
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- NII Book ID
- AA10885497
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- COI
- 1:STN:280:DC%2BD1cvovF2jtg%3D%3D
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- ISSN
- 13475215
- 09186158
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- NDL BIB ID
- 9587341
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- CiNii Articles
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- Abstract License Flag
- Disallowed