| Project/Area Number |
20591380
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | St.Marianna University School of Medicine |
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Principal Investigator |
OSADA Kenichi St.Marianna University School of Medicine, 医学部, 講師 (20233504)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Mituhiko 国立精神・神経センター 精神保健研究所, 精神薬理研究部, 部長 (60240040)
KIDA Satoshi 東京農業大学, 用生物科学部, 教授 (80301547)
MIYOSHI Hiroshi 聖マリアンナ医科大学, 医学部, 講師 (80322519)
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| Co-Investigator(Renkei-kenkyūsha) |
ASAKURA Mikio 聖マリアンナ医科大学, 医学部, 准教授 (70103504)
MATUI Hiroaki 聖マリアンナ医科大学, 医学(系)研究科(研究院), 教授 (90181685)
KATOU Tomohiro 聖マリアンナ医科大学, 医学部, 教授 (80233807)
SASUGA Yasuo 聖マリアンナ医科大学, 医学部, 助教 (60308450)
MISONOO Atushi 聖マリアンナ医科大学, 医学部, 助教 (20410128)
GAWA Yuriko 聖マリアンナ医科大学, 医学部, 研究技術員 (90449398)
TANAKA Daisuke 聖マリアンナ医科大学, 医学部, 助教 (80410124)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | SNRI / dynamin / GTPase |
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| Research Abstract |
Dynamin (Dyn) 1 plays a role in recycling of synaptic vesicles, and thus in nervous system function. Fluvoxamine , a selective serotonin reuptake inhibitor (SSRI),may compete with L-phosphatidylserine (PS) for binding to the pleckstrin homology domain of dynamin I (Dyn 1) GTPase. On the other hand, sertraline was a mixed type inhibitor with respect to both GTP and PS. We showed that sertraline is a mixed-type inhibitorof Dyn 1 with respect to both GTP and L-a-phosphatidyl-L-serine (PS) in vitro, and we suggested that it may regulate the neurotransmitter transport by modulating synaptic vesicle endocytos is via inhibition of Dyn 1 GTPase. GTPase assay showed that sertraline inhibited Dyn 2 as well as Dyn 1. Therefore, the effect of sertraline on endocytosis was mediated by Dyn 2, at least in HeLa cells, as well as by Dyn 1 in cell lines that express it. Moreover, the inhibition mechanism of transferrin (Tf) uptake by sertraline differed from that in cells expressing Dyn 1 K44A, a GTP binding-defective variant.
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