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Molecular mechanism for anti-thrombotic action of alcohol drinking related to TRP channels of platelets.

Research Project

Project/Area Number 22590562
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hygiene
Research InstitutionHyogo Medical University

Principal Investigator

MARUMO Mikio  兵庫医科大学, 医学部, 講師 (40333950)

Co-Investigator(Kenkyū-buntansha) WAKABAYASHI Ichiro  兵庫医科大学, 医学部, 教授 (70220829)
TAKEDA Yuji  山形大学, 医学部, 助教 (90302299)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2010: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords予防医学 / 血栓症 / アルコール
Research Abstract

The mechanism for the inhibitory action of alcohol on platelet aggregation is unknown. In this study, effects of ethanol and methanol on capacitative Ca2+ entry and the subsequent aggregation and diacylglycerol-dependent Ca2+ entry and the subsequent aggregation in platelets were investigated. Both Ca2+ entry pathways are known to be mediated by TRP channels. Aggregation of washed platelets was significantly inhibited by ethanol irrespective of the kind of stimulant for platelets, and similar inhibition was found in platelets in the whole blood by using the modified SFP method. On the other hand, capacitative Ca2+ entry and diacylglycerol-dependent Ca2+ entry were significantly inhibited and augmented, respectively, by ethanol. Therefore, ethanol showed diverse effects on Ca2+ entry through different mechanisms such as intracellular Ca2+-store depletion and stimulation by diacylglycerol. Consequently, thrombin-induced Ca2+ entry, which is thought to be the sum of the above two knds of Ca2+ entry, was not significantly altered by ethanol. Methanol showed no significant effects on capacitative Ca2+ entry and diacylglycerol-dependent Ca2+ entry, while thrombin-induced platelet aggregation was significantly augmented by methanol. Thus, the effects of alcohol on platelet function vary with the kind of alcohol as well as the kind of stimulant.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (23 results)

All 2013 2012 2011 2010

All Journal Article (7 results) (of which Peer Reviewed: 3 results) Presentation (16 results) (of which Invited: 1 results)

  • [Journal Article] 血小板のカルシウム流入および凝集能へのアルコール類の作用.2012

    • Author(s)
      丸茂幹雄, 丸茂久美子, 若林一郎.
    • Journal Title

      アルコールと医学生物学

      Volume: 31 Pages: 103-7

    • URL

      http://www.toyoshoten.co.jp/

    • Related Report
      2012 Final Research Report
  • [Journal Article] Inhibition of thrombin-induced Ca^^<2+> influx in platelets by R59949, an inhibitor of diacylglycerol kinase2012

    • Author(s)
      Marumo M, Nakano T, Takeda Y, Goto K, Wakabayashi I.
    • Journal Title

      J Pharm Pharmacol

      Volume: 64 Issue: 6 Pages: 855-861

    • DOI

      10.1111/j.2042-7158.2012.01485.x

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] 血小板のカルシウム流入および凝集能へのアルコール類の作用2012

    • Author(s)
      丸茂幹雄, 丸茂久美子, 若林一郎
    • Journal Title

      アルコールと医学生物学

      Volume: 31 Pages: 103-7

    • Related Report
      2012 Annual Research Report
  • [Journal Article] エタノールの血小板抑制作用に関する異なった測定法による評価;2011

    • Author(s)
      丸茂幹雄, 丸茂久美子, 若林一郎
    • Journal Title

      アルコールと医学生物学

      Volume: 30 Pages: 84-87

    • URL

      http://www.toyoshoten.co.jp/

    • Related Report
      2012 Final Research Report
  • [Journal Article] エタノールの血小板抑制作用に関する異なった測定法による評価2011

    • Author(s)
      丸茂幹雄, 丸茂久美子, 若林一郎
    • Journal Title

      アルコールと医学生物学

      Volume: 30 Pages: 84-87

    • Related Report
      2011 Annual Research Report
  • [Journal Article] Diverse* *70* *605040300 0.5 12Methanol (%)effects of ethanol on Ca2+ entry and subsequentaggregation of platelets.2010

    • Author(s)
      Marumo M, Wakabayashi I.
    • Journal Title

      Alcohol;

      Volume: 44(4) Issue: 4 Pages: 343-50

    • DOI

      10.1016/j.alcohol.2010.02.002

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Diverse effects of ethanol on Ca^<2+> entry and subsequent aggregation of platelets.2010

    • Author(s)
      Marumo M, Wakabayashi I.
    • Journal Title

      Alcohol

      Volume: 44 Pages: 343-350

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] DGKインヒビター、R59949によるトロンビン惹起カルシウム流入の抑制効果2013

    • Author(s)
      丸茂幹雄、中野知之、武田裕司、後藤薫、若林一郎
    • Organizer
      第35回日本血栓止血学会
    • Place of Presentation
      山形
    • Year and Date
      2013-06-01
    • Related Report
      2012 Final Research Report
  • [Presentation] 全血中での血小板凝 集へのエタノールの抑制作用;2013

    • Author(s)
      丸茂幹雄、若林一郎
    • Organizer
      第32回アルコル医 学生物 学研究会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2013-01-26
    • Related Report
      2012 Final Research Report
  • [Presentation] アルコールによる血 小板機能抑制作用のメカニズム;2012

    • Author(s)
      丸茂幹雄、若林一郎
    • Organizer
      第82回日本衛生学会
    • Place of Presentation
      京都
    • Year and Date
      2012-03-25
    • Related Report
      2012 Final Research Report
  • [Presentation] アルコールによる血小板機能抑制作用のメカニズム2012

    • Author(s)
      丸茂幹雄、若林一郎
    • Organizer
      第82回日本衛生学会
    • Place of Presentation
      京都
    • Year and Date
      2012-03-25
    • Related Report
      2011 Annual Research Report
  • [Presentation] 血小板のカルシウム 流入および凝集能へのアルコール類の作用;2012

    • Author(s)
      丸茂幹雄、若林一郎
    • Organizer
      第31回アルコール医学生物学研究会学術集会
    • Place of Presentation
      金沢
    • Year and Date
      2012-01-28
    • Related Report
      2012 Final Research Report
  • [Presentation] 血小板のカルシウム流入および凝集能へのアルコール類の作用2012

    • Author(s)
      丸茂幹雄、若林一郎
    • Organizer
      第31回アルコール医学生物学研究会
    • Place of Presentation
      金沢
    • Year and Date
      2012-01-28
    • Related Report
      2011 Annual Research Report
  • [Presentation] Effects ofAlcohol on Ca2+ Entry and SubsequentAggregation of Platelets Through Different Pathways.2012

    • Author(s)
      M. Marumo; I. Wakabayashi
    • Organizer
      (Symposium) 16th Congress of International Society for Biomedical Research on Alcoholism.
    • Place of Presentation
      Sapporo, Japan
    • Related Report
      2012 Final Research Report
  • [Presentation] Effects of Ethanol on Ca2+ Entry and Aggregation of Platelets Through Different Signal Transduction Pathways.2012

    • Author(s)
      M. Marumo; I. Wakabayashi
    • Organizer
      16th Congress of International Society for Biomedical Research on Alcoholism.
    • Place of Presentation
      Sapporo, Japan
    • Related Report
      2012 Final Research Report
  • [Presentation] Effects of alcohol on Ca2+ entry and subsequent aggregation of platelets through different pathways. (Symposium)2012

    • Author(s)
      Marumo M, Wakabayashi I
    • Organizer
      The 16th Congress of International Sociery for Biomedical Research on Alcoholosm (ISBRA2012)
    • Place of Presentation
      Sapporo
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Effects of Ethanol on Ca2+ Entry and Aggregation of Platelets Through Different Signal Transduction Pathways.2012

    • Author(s)
      M. Marumo; I. Wakabayashi
    • Organizer
      The 16th Congress of International Sociery for Biomedical Research on Alcoholosm (ISBRA2012)
    • Place of Presentation
      Sapporo
    • Related Report
      2012 Annual Research Report
  • [Presentation] 異なった機序に基づく血小板凝集能測定におけるエタノールの血小板凝集抑制効果;2010

    • Author(s)
      丸茂幹雄、若林一郎
    • Organizer
      第30回アルコール医学生物学研究会
    • Place of Presentation
      久留米
    • Year and Date
      2010-11-26
    • Related Report
      2012 Final Research Report
  • [Presentation] 異なった機序に基づく血小板凝集能測定におけるエタノールの血小板凝集抑制効果2010

    • Author(s)
      丸茂幹雄、若林一郎
    • Organizer
      第30回アルコール医学生物学研究会
    • Place of Presentation
      久留米
    • Year and Date
      2010-11-26
    • Related Report
      2010 Annual Research Report
  • [Presentation] 血小板のカルシウム流入機構へのエタノールの異なった作用;2010

    • Author(s)
      丸茂幹雄、若林一郎
    • Organizer
      第45回日本アルコール薬物医学会
    • Place of Presentation
      小倉
    • Year and Date
      2010-10-09
    • Related Report
      2012 Final Research Report
  • [Presentation] 血小板のカルシウム流入機構へのエタノールの異なった作用2010

    • Author(s)
      丸茂幹雄、若林一郎
    • Organizer
      第45回日本アルコール薬物医学会
    • Place of Presentation
      小倉
    • Year and Date
      2010-10-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] 血小板の異なるメカニズムを介するカルシウム流入および凝集能へのアルコールの作用;2010

    • Author(s)
      丸茂幹雄、若林一郎
    • Organizer
      第33回日本血栓止血学会
    • Place of Presentation
      鹿児島
    • Year and Date
      2010-04-24
    • Related Report
      2012 Final Research Report
  • [Presentation] 血小板の異なるメカニズムを介するカルシウム流入および凝集能へのアルコールの作用2010

    • Author(s)
      丸茂幹雄、若林一郎
    • Organizer
      第33回日本血栓止血学会
    • Place of Presentation
      鹿児島
    • Year and Date
      2010-04-24
    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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