1986 Fiscal Year Final Research Report Summary
Effects of Calmodulin Antagonists on phospholipid Metabolism in Platelets
| Project/Area Number |
60570089
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General pharmacology
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| Research Institution | Kyoto University |
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Principal Investigator |
FUJIWARA Motokazu Kyoto University, 医学部, 助手 (60093308)
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| Project Period (FY) |
1985 – 1986
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| Keywords | Platelet / Phospholipid / Calcium / カルモジュリン |
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| 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
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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
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Research Products
(8 results)
