• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Establishment of the platelet disorders characterized by impaired signal transduction

Research Project

Project/Area Number 14570968
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionNIIGATA UNIVERSITY

Principal Investigator

FUSE Ichiro  NIIGATA UNIVERSITY, Medical and Dental Hospital, Associate Professor, 医歯学総合病院, 助教授 (90242429)

Co-Investigator(Kenkyū-buntansha) TOBA Ken  NIIGATA UNIVERSITY, Medical and Dental Hospital, Lecturer, 医歯学総合病院, 講師 (60313540)
FURUKAWA Tatsuo  NIIGATA UNIVERSITY, Medical and Dental Hospital, Associate Professor, 医歯学総合病院, 助教授 (00272849)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsthromboxane receptor / ADP receptor / P2X1 receptor / F2Y12 receptor / Platelet signal transduction disease / 血小板刺激伝達異常性
Research Abstract

Ca^<2+> ionophores such as A23187 and ionomycin, which transport divalent cations across membranes, were reported to induce platelet activation. Several evidences suggested that secretion and phospholipase C activation induced by Ca^<2+> ionophore are totally dependent upon intact thromboxane. This suggests that platelets with impaired thromboxane formation or impaired response to thromboxane show defective Ca^<2+> ionophore-induced platelet aggregation. In fact, we previously reported that Ca^<2+> ionophore A23187-induced platelet aggregation was markedly reduced in patients with congenital platelet cyclo-oxygenase or with defective TXA_2-induced platelet aggregation. As to the latter disorder, we clarified that Arg^<60> to Leu mutation in the first cytoplasmic loop of the TXA_2 receptor(TXR) causes impaired coupUng between TXR and phoshoplipase C activation.
On the other hand, several cases with bleeding tendencies whose platelets respond defectively to Ca^<2+> ionophore without those causes have been reported However, since these cases are rare, the defective site has not been fully elucidated.
We analyzed the effect of PGE_1-induced increase in platelet cAMP levels and its inhibition by ADP and epinephrine hi three patients characterized by impaired ADP-induced platelet aggregation. We found that ADP as well as epinephrine lowered the PGE_1-induced cAMP increase in the patient's platelets. This suggests that the patient does not have a defect of the platelet P2Y_<12> receptor for ADP, since, in the patients with this defect, it was reported that epinephrine normally lowered the PGE_1-stimulated platelet cAMP increase, but ADP was without effect. These findings suggest that the defective site in the patients' platelets lies in the process distal to or independent of protein kinase C activation, Ca^<2+> mobilization and MLC phosphorylation.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Ichiro Fuse, et al.: "DDAVP normalized the bleeding time in patients with congenital thromboxane A_2 receptor abnormality"Transfusion. 43. 563-567 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miwako Narita, et al.: "Ca^<2+> ionophore-induced dendritic cell differentiation in a patient with defective Ca^<2+> ionophore-induced platelet aggregation."British Journal of Haematology. 120. 910-911 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ichiro Fuse, et al.: "DDAVP normalized the bleeding time in patients with platelet disorder characterized by defective calcium ionophore-induced platelet aggregation"British Journal of Haematology. 122. 870-871 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 布施一郎: "血小板機能異常症-トロンボキサンA_2不応症"総合臨床. 52. 1643-1646 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 布施一郎: "血小板トロンボキサン受容体とシグナル伝達異常症-トロンボキサン受容体異常症を中心として-"医学のあゆみ. 208. 203-206 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 布施一郎: "血小板とと生理活性物質"金芳堂. 182 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fuse I, et al.: "DDAVP normalized the bleeding time in patients with congenital thramboxane A_2 receptor abnormality."Transfusion. 43. 563-567 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Narita M, et al.: "Ca^<2+> ionophore-induced dendritic cell differentiation in a patient with defective Ca^<2+> ionophore-induced platelet aggregation."British J Haematol. 120. 910-911 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fuse I et al.: "DDAVP normalized the bleeding time in patients with platelet disorder characterized by defective calcium ionophore-induced platelet aggregation."British J Haematol. 122. 870-871 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fuse I: "Congenital thrombhoxane receptor abnormality"SOGORINSYO. 52. 1643-1646 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fuse I: "Platelet signal transduction defect through the thromboxane A_2 Receptor-special reference to congenital platelet thromboxane A_2 receptor abnormality"GAKU NO AYUMI. 208. 203-206 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fuse I: "Platelet thromboxane receptor and platelet signal transduction disease."Platelets and Biological Active ompounds, (KINPODO). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ichiro Fuse, et al.: "DDAVP normalized the bleeding time in patients with congenital thromboxane A_2 receptor abnormality"Transfusion. 43. 563-567 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Miwako Narita, et al.: "Ca^<2+> ionophore-induced dendritic cell differentiation in a patient with defective Ca^<2+> ionophore-induced platelet aggregation"British Journal of Haematology. 120. 910-911 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ichiro Fuse, et al.: "DDAVP normalized the bleeding time in patients with platelet disorder characterized by defective calcium ionophore-induced platelet aggregation"British Journal of Haematology. 122. 870-871 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 布施一郎: "血小板機能異常性-トロンボキサンA_2不応症"総合臨床. 52. 1643-1646 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 布施一郎: "血小板トロンボキサン受容体とシグナル伝達異常症-トロンボキサン受容体異常症を中心として-"医学のあゆみ. 208. 203-206 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 布施一郎: "血小板生物学"メディカルレビュー社(2004年発行予定). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ichiro Fuse: "DDAVP normalized the bleeding time in patients with congenital thromboxane A_2 receptor abnormality"Transfusion. 43. 563-567 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ichiro Fuse: "DDAVP normalized the bleeding time in patients with platelet disorder characterized by defective calcium ionophore-induced platelet"British Journal of Haematology. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] 布施一郎: "血小板と生理活性物質(尾崎由起男、池田康夫、島田和幸、高井義美、丸山征郎編集)、金芳堂"血小板トロンボキサン受容体とシグナル伝達異常症. 182 (2002)

    • Related Report
      2002 Annual Research Report

URL: 

Published: 2002-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi