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Effects of Calmodulin Antagonists on phospholipid Metabolism in Platelets

Research Project

Project/Area Number 60570089
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field General pharmacology
Research InstitutionKyoto University

Principal Investigator

FUJIWARA Motokazu  Kyoto University, 医学部, 助手 (60093308)

Project Period (FY) 1985 – 1986
Project Status Completed (Fiscal Year 1986)
Budget Amount *help
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1986: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1985: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsPlatelet / Phospholipid / Calcium / カルモジュリン
Research Abstract

<Ca^(2+)> is essential for platelet activation, with effecting on the degradation of membrane phospholipids by phospholipase <A_2> or phospholipase C. On the other hand, <Ca^(2+)> also regulate the synthesis of main constituent phospholipid, phosphatidylcholine(PC), phosphatidylethanolamine(PE) and phosphatidyl-serine(PS). In this study, the effects of <Ca^(2+)> , calmodulin and calmodulin antagonists on phospholipid synthesis were examined using rabbit platelets. PS is demonstrated to be synthesized by <Ca^(2+)> -dependent phospholipid base-exchange reactions. In washed rabbit platelets, calmodulin antagonists (chlorpromazine, W-7, etc) stimulated serine base-exchange reaction, accompanied with decrease of free serine and increase of free ethanolamine and choline in platelets. However, in platelet membrane fractions, these calmodulin antagonists stimulated not only serine base-exchange reaction, but also ethanolamine and choline base-exchange reactions. These three base-exchange react … More ions were inhibited by other two bases, respectively. We measured the contents of the three bases in platelets and calculated the concentrations of them. Under the co-existence of the three bases at the calculated concentrations, serine base-exchange activity was the highest. The sum of triangle competition of the three bases seemed to be the reason that only serine base-exchange reaction was stimulated by calmodulin antagonists in washed platelets. PE and PC are also synthesized by CDP-pathway, from CDP-ethanolamine or CDP-choline with metal cofactor of <Mg^(2+)> , <Co^(2+)> or <Mn^(2+)> . When <Mg^(2+)> was used as a cofactor, the inhibitory effect was the most remarkable. These inhibitory effects seemed to be mediated directly by <Ca^(2+)> , which interacted with specific metal cofactor binding site(s) of the enzymes. It has been demonstrated that <Ca^(2+)> is essential to platelet aggregation and calmodulin antagonists inhibit platelet aggregation. It is suggested that <Ca^(2+)> and calmodulin antagonists affect the platelet function by regulating not only the phospholipid degradation, but also the phospholipid synthesis in platelets. Less

Report

(1 results)
  • 1986 Final Research Report Summary
  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Morikawa,Shigehiro: Thrombosis Reseach. 37. 267-278 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Fujiwara,Motokazu: Journal of Biochemistry. 99. 615-625 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Taniguchi,Shinkichi: Journal of Biochemistry. 100. 485-491 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Morikawa,Shigehiro: Biochemical Pharmacology. 35. 4473-4477 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Morikawa, Shigehiro: "Effects of Calmodulin Antagonists and Calmodulin on Phospholipid Base-Exchange Activities in Rabbit Platelets." Thrombosis Research. 37. 267-278 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Fujiwara, Motokazu: "Effects of Calmodulin Antagonists on Serine Phospholipid Base-Exchange Reaction in Rabbit Platelets." Journal of Biochemistry. 99. 615-625 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Taniguchi, Shinkichi: "Effects of <Ca^(2+)> on Ethanolaminephosphotransferase and Cholinephosphotransferase in Rabbit Platelets." Journal of Biochemistry. 100. 485-491 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Morikawa, Shigehiro: "Stimulatory Effect of Calmodulin Antagonists on Phospholipid Base-Exchange Reactions in Rabbit platelet membranes." Biochemical Pharmacology. 35. 4473-4477 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary

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Published: 1987-03-31   Modified: 2016-04-21  

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