| Project/Area Number |
01570626
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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 |
内分泌・代謝学
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| Research Institution | Chiba University |
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Principal Investigator |
HIRAI Aizan Chiba University, Department of Medicine Assistant, 医学部附属病院, 助手 (10189813)
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| Co-Investigator(Kenkyū-buntansha) |
TAMURA Yasushi Chiba University, Department of Medicine Associate Professor, 医学部, 助教授 (90009671)
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| Project Period (FY) |
1989 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1990: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1989: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | EPA / 11-dehydro-TXB2 / 2, 3-dinor-6-ketoPGF_1 alpha / Platelets / 魚脂多価不飽和脂肪酸 / EPA / 家族性高コレステロ-ル血症 / プロスタサイクリン / トロンボキサンA_2 / 多価不飽和脂肪酸 / エイコサペンタエン酸 / ドコサヘキサエン酸 |
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| Research Abstract |
The effect of changes in platelet membrane cholesterol content on thromboxane A_2(TXA_2)-induced platelet activation was studied. Concentrations of 9,11-epithio-11,12-methano-TXA_2 (STA_2), a stable analogue of TXA_2 which can cause half-maximal aggregation and release of [^<14>C] serotonin in cholesterol-rich platelets were significantly lower than those in cholesterol-normal platelets. STA_2-induced increase in cytosolic calcium concentration and [^<32>P] phosphatidic acid formation in cholesterol-rich platelets were significantly greater than those in cholesterol-normal platelets. The maximal concentration of binding site for SQ29548 was signifi-cantly increased in cholesterol-rich platelets compared with cholesterol-normal platelets, while the effect of changes in platelet membrane cholesterol content on thromboxane A_2(TXA_2)-induced platelet activation was studied. Concentrations of 9,11-epithio-11,12-methano-TXA_2 (STA_2), a stable analogue of TXA_2 which can cause half-maximal aggregation and release of [^<14>] serotonin in cholesterol-rich platelets were significantly lower than those in cholesterol-normal platelets. STA_2-induced increase in cytosolic calcium concentration and [^<32>P] phosphatidic acid formation in cholesterol-rich platelets were significantly greater than those in cholesterol-normal platelets. The maximal concentration of binding site for SQ29548 was significantly increased in cholesterol-rich platelets compared with cholesterol-normal platelets, while the equilibrium dissociation rate constant for SQ29548 did not differ between cholesterol-rich and cholesterol-normal platelets. The present study suggested that sensitivity to TXA2 was increased by the incorporation of cholesterol into platelet membrane and that the cause of hyper-sensitivity to TXA_2 in cholesterol-rich platelets may be partly explained by an increase in binding capacity for TXA_2.
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