Rittenhouse S E
Biochem J. 1984 Aug 15;222(1):103-10. doi: 10.1042/bj2220103.
Human platelets exposed to the Ca2+ ionophore A23187 form cyclo-oxygenase metabolites from liberated arachidonic acid and secrete dense granule substituents such as ADP. I have shown previously that A23187 causes activation of phospholipase A2 and some stimulation of phospholipase C. I now report that, in contrast to the case for thrombin, the activation of phospholipase C in response to ionophore is completely dependent upon the formation of cyclo-oxygenase products and the presence of ADP. The addition of A23187 to human platelets induces a transient drop in the amount of phosphatidylinositol 4,5-bisphosphate, a decrease in the amount of phosphatidylinositol, and the formation of diacylglycerol and phosphatidic acid. In addition, lysophosphatidylinositol and free arachidonic acid are produced. The presence of cyclo-oxygenase inhibitors or agents which remove ADP partially impairs these changes. When both types of inhibitor are present, the changes in phosphatidylinositol 4,5-bisphosphate and the formation of diacylglycerol and phosphatidic acid are blocked entirely, whereas formation of lysophosphatidylinositol and free arachidonic acid are relatively unaffected. The prostaglandin H2 analogue U46619 activates phospholipase C. This stimulation is inhibited partially by competitors for ADP. I conclude that phospholipase C is not activated by Ca2+ in the platelet, and suggest that stimulation is totally dependent upon a receptor coupled event.
暴露于钙离子载体A23187的人血小板会从释放的花生四烯酸中形成环氧化酶代谢产物，并分泌致密颗粒成分如ADP。我之前已经表明，A23187会导致磷脂酶A2的激活以及对磷脂酶C的一些刺激。我现在报告，与凝血酶的情况相反，离子载体引起的磷脂酶C的激活完全依赖于环氧化酶产物的形成和ADP的存在。向人血小板中添加A23187会导致磷脂酰肌醇4,5-二磷酸量的短暂下降、磷脂酰肌醇量的减少以及二酰基甘油和磷脂酸的形成。此外，还会产生溶血磷脂酰肌醇和游离花生四烯酸。环氧化酶抑制剂或去除ADP的试剂的存在会部分损害这些变化。当两种类型的抑制剂都存在时，磷脂酰肌醇4,5-二磷酸的变化以及二酰基甘油和磷脂酸的形成会被完全阻断，而溶血磷脂酰肌醇和游离花生四烯酸的形成相对不受影响。前列腺素H2类似物U46619会激活磷脂酶C。这种刺激会被ADP的竞争性抑制剂部分抑制。我的结论是血小板中的磷脂酶C不会被钙离子激活，并表明刺激完全依赖于受体偶联事件。
