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Effect of anticancer drugs on 5-HT3 receptor subunits

Research Project

Project/Area Number 24659748
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Otorhinolaryngology
Research InstitutionOsaka University

Principal Investigator

SHIMADA Shoichi  大阪大学, 医学(系)研究科(研究院), 教授 (20216063)

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)
Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
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)
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
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.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (14 results)

All 2014 2013 2012

All Journal Article (6 results) (of which Peer Reviewed: 3 results) Presentation (8 results)

  • [Journal Article] 5-HT(3) receptor expression in the mouse vestibular ganglion2014

    • Author(s)
      Takimoto Y, Ishida Y, Nakamura Y, Kamakura T, Yamada T, Kondo M, Kitahara T, Uno A, Imai T, Horii A, Okazaki S, Nishiike S, Inohara H, Shimada S
    • Journal Title

      Brain Res

      Volume: 1157 Pages: 74-82

    • Related Report
      2013 Final Research Report
  • [Journal Article] The 5-HT3A receptor is essential for fear extinction2014

    • Author(s)
      Kondo M, Nakamura Y, Ishida Y, Yamada T, Shimada S
    • Journal Title

      Learn Mem

      Volume: 21(1) Pages: 1-4

    • Related Report
      2013 Final Research Report
  • [Journal Article] 5-HT3 receptor expression in the mouse vestibular ganglion2014

    • Author(s)
      Takimoto Y, Ishida Y, Nakamura Y, Kamakura T, Yamada T, Kondo M, Kitahara T, Uno A, Imai T, Horii A, Okazaki S, Nishiike S, Inohara H, Shimada S
    • Journal Title

      Brain Res

      Volume: 1557 Pages: 74-82

    • DOI

      10.1016/j.brainres.2014.02.016

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Subunit-dependent inhibition and potentiation of 5-HT3 receptor by the anticancer drug, topotecan2013

    • Author(s)
      Nakamura Y, Ishida Y, Yamada T, Kondo M, Shimada S
    • Journal Title

      J Neurochem

      Volume: 125(1) Pages: 7-15

    • Related Report
      2013 Final Research Report
  • [Journal Article] Subunit-dependent inhibition and potentiation of 5-HT3 receptor by the anticancer drug, topotecan” Journal of neurochemistry2013

    • Author(s)
      Yukiko Nakamura
    • Journal Title

      Journal of neurochemistry

      Volume: 125(1) Issue: 1 Pages: 7-15

    • DOI

      10.1111/jnc.12146

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The 5-HT3A receptor is essential for fear extinction.2013

    • Author(s)
      Kondo M, Nakamura Y, Ishida Y, Yamada T, Shimada S
    • Journal Title

      Learn Mem

      Volume: 21 Issue: 1 Pages: 1-4

    • DOI

      10.1101/lm.032193.113

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] 抗癌剤による5- HT3受容体への直接作用2014

    • Author(s)
      中村雪子、石田雄介、近藤誠、島田昌一
    • Organizer
      第119回日本解剖学会総会全国学術集会
    • Place of Presentation
      栃木
    • Related Report
      2013 Final Research Report
  • [Presentation] 抗癌剤による5-HT3受容体への直接作用2014

    • Author(s)
      中村雪子、石田雄介、近藤 誠、島田昌一
    • Organizer
      第119回日本解剖学会総会全国学術集会
    • Place of Presentation
      栃木
    • Related Report
      2013 Annual Research Report
  • [Presentation] Direct modification of 5- HT3 receptor by anti- cancer drugs2013

    • Author(s)
      Yukiko Nakamura, Yusuke Ishida, Makoto Kondo, Shoichi Shimada
    • Organizer
      第56回日本神経科学会大会
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report
  • [Presentation] 抗癌剤トポテカンによるセロトニン3受容体のサブユニットに依存した応答調節2013

    • Author(s)
      中村雪子、石田雄介、山田貴博、近藤誠、島田昌一
    • Organizer
      第118回日本解剖学会総会
    • Place of Presentation
      香川県高松市かがわ国際会議場
    • Related Report
      2013 Final Research Report
  • [Presentation] Direct modification of 5-HT3 receptor by anti-cancer drugs.2013

    • Author(s)
      Yukiko Nakamura, Yusuke Ishida, Makoto Kondo, Shoichi Shimada
    • Organizer
      第56回日本神経科学会大会
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] 抗癌剤トポテカンによるセロトニン3受容体のサブユニットに依存した応答調節2013

    • Author(s)
      中村雪子、石田雄介、山田貴博、近藤誠、島田昌一
    • Organizer
      第118回日本解剖学会総会
    • Place of Presentation
      香川県高松市かがわ国際会議場
    • Related Report
      2012 Research-status Report
  • [Presentation] Subunit-dependent inhibition and potentiation of 5-HT3 receptor by the anticancer drug, topotecan. The 11th Biennial Meeting of the Asian-Pacific Society for Neurochemistry2012

    • Author(s)
      Y. Nakamura, Y. Ishida, T. Yamada, M. Kondo, S. Shimada
    • Organizer
      55th Annual Meeting of the Japanese Society for Neurochemistry
    • Place of Presentation
      Kobe, Japan
    • Related Report
      2013 Final Research Report
  • [Presentation] Subunit-dependent inhibition and potentiation of 5-HT3 receptor by the anticancer drug, topotecan2012

    • Author(s)
      Y. Nakamura, Y. Ishida, T. Yamada, M. Kondo, S. Shimada
    • Organizer
      The 11th Biennial Meeting of the Asian-Pacific Society for Neurochemistry / 55th Annual Meeting of the Japanese Society for Neurochemistry
    • Place of Presentation
      Kobe, Japan
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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