血液と脈管
Online ISSN : 1884-2372
Print ISSN : 0386-9717
cAMP, cGMPによる血小板活性化調節機構の解析
IP3産生とCa2+動態に対する抑制効果
中島 茂東松 豊彦服部 浩明岡野 幸雄野沢 義則
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1986 年 17 巻 1 号 p. 59-61

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In many secretory cells, cyclic nucleotides and Ca2+ cooperatively or antagonistically control cell responses. Activation of platelets with thrombin caused a rapid breakdown of phosphoinositides and an increase of cytoplasmic free Ca2+ concentration, which resulted in shape change, secretion and aggregation. The hypothetical concept has recently been proposed that inositol trisphosphate, a degradation product of phosphatidylinositol 4, 5-bisphosphate (PIP2), serves as a second messenger for mobilizing intracellular Ca2+. The effects of cAMP and cGMP on thrombin-induced human pletelet responses were investigated. Thrombin-induced serotonin secretion and aggregation were inhibited by pretreatment with dibutyryl cAMP (dbcAMP) or 8-bromo cGMP (8bcGMP) in a dose-dependent manner. However, shape change was not affected by 8bcGMP. Preincubation of platelets with dbcAMP or 8bcGMP was without effect on the basal level of inositol trisphosphate and free cytosolic Ca2+, measured by fluorescent indicator quin 2, but suppressed their thrombin-induced enhancements. Enhanced [32P] incorporation into phosphatidylinositol 4-phosphate (PIP) and PIP2 was observed with dbcAMP or 8bcGMP treatment, suggesting activation of PI- and PIP-kinases. These results indicate that cGMP as well as cAMP acts as a negative messenger to prevent platelet activation. The inhibitory effect can be explained at least in part by the repression of phospholipase activation, resulting in reduced formation of inositol trisphosphate.

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