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Mechanism of metabolites produced by and protective drugs against ischemia-reperfusion injury in ventricular myocytes.

Research Project

Project/Area Number 10670078
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionAKITA UNIVERSITY (1999)
Asahikawa Medical College (1998)

Principal Investigator

YAZAWA Kazuto  School of Medicine, akita Univeersity, Lecturer, 医学部, 講師 (90212274)

Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywordscalcium current / lysophosphatidylcholine / ventricular myocytes / patch clamp method / guinea-pig / バッチクランプ法
Research Abstract

Lysophosphatidylcholine (LPC), an amphiphilic metabolite of membrane phospholipids, accumulates in cardiac tissue during ischemia and reperfusion. LPC produces arrythmia, although the effect for ion channels is not fully understood under the physiological and pathophysiological conditions. The aim of this study was to investigate the mechanisms underlying the effect of LPC on CaィイD12+ィエD1 current (IィイD2CaィエD2 under these conditions in single ventricular cells using the whole-cell patch clamp method.
Single ventricular myocytes of a female guinea-pig (300-600g) were prepared by using a Langendorff method. The concentration of CaィイD12+ィエD1 in the pipette solutions at pH 7.4 and pH 6.4 were pCa 8. The external solutions were warmed by water jacket before being put into the recording chamber ; all experiments were performed at 35-37℃.
The results were followed : 1. LPC reduced IィイD2CaィエD2 under the physiological and pathophysiological pH ; 2. The sensitivity of IィイD2CaィエD2 for LPC was increased under acidic conditions ; 3. Although LPC caused depression of IィイD2CaィエD2 without affecting the activation curve or the steady-state inactivation curve at physiological pH, LPC shifted them in the negative direction at pathophysiological pH.
These results suggest the following possibilities ; 1. protons increase the inhibitory effect of LPC on IィイD2CaィエD2 ; 2. LPC might increase the proton sensitivity of the inside membrane, or decreases the proton sensitivity of the outside membrane.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (6 results)

All Other

All Publications (6 results)

  • [Publications] MA,H.: "Protective effect of quinaprilat, an active metabolite of auinapril, on Ca^<2+>_overload induced by lysophosphatidylcholine in isolated rat cardiomyocytes"Jpn. J. Plarmacol.. 79. 17-24 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] HASHIZUME,H: "A new approach to the development of anti-ischemic drugs : Protective drugs against cell injury induced by llysophosphatidylcholine"Life Science. 62. 1695-1699 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] MA, H.: "Protective effect of quinaprilat, an active metabolite of auinapril, on CaィイD12+ィエD1-overload induced by lysophosphatidylcholine in isolated rat cardiomyocytes."Jpn. J. Pharmacol.. 79. 17-24 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] HASHIZUME, H: "A new approach to the development of anti-ischemic drugs : Protective drugs against cell injury induced by lysophosphatidylcholine."Life Science. 62. 1695-1699 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ma, H., Hashizume, H., Hara, A., Yazawa, K. & Abiko, Y.: "Protective effect of quinaprilat, an active metabolite of auinapril, on Ca^<2+>-overload induced by lysophosphatidylcholine in isolated rat cardiomyocytes"Jpn. J. Plarmacol.. 79. 17-24 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hashizume, H., Chen, M., Ma, H., Hara, A., Yazawa, K., Xiao, C.Y. & Abiko, Y.: "A new approach to the development of anti-ischemic drugs : Protective drugs against cell injury induced by lysophosphatidylcholine"Life Science. 62. 1695-1699 (1998)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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