| Project/Area Number |
24659748
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Osaka University |
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Principal Investigator |
SHIMADA Shoichi 大阪大学, 医学(系)研究科(研究院), 教授 (20216063)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIDA Yusuke 大阪大学, 大学院医学系研究科, 講師 (30381809)
NAKAMURA Yukiko 大阪大学, 大学院医学系研究科, 助教 (90548083)
YAMADA Takahiro 大阪大学, 大学院医学系研究科, 助教 (40601597)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 化学療法 / 5-HT3受容体 / 抗がん剤 / セロトニン / 悪心 / 嘔吐 / 抗癌剤 |
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| Research Abstract |
The 5-hydroxytryptamine (serotonin) type 3 (5-HT3) receptor belongs to the superfamily of Cys-loop ligand-gated ion channels, and can be either homopentameric (5-HT3A) or heteropentameric (5-HT3AB) receptor. We showed that the anticancer drug, topotecan, bidirectionally modulates the 5-HT3 receptor using a voltage clamp technique. Topotecan inhibited 5-HT-gated current through homomeric 5-HT3A receptors. On the other hand, additional expression of the 5-HT3B subunit changed the response to topotecan from an inhibitory to a potentiatory one. Furthermore, the effect was reduced in the receptors containing the 5-HT3B (Y129S) polymorphic variant. These finding could explain individual differences in the sensitivity to topotecan-induced nausea and vomiting.
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