Activation of human platelet phospholipase C by ionophore A23187 is totally dependent upon cyclo-oxygenase products and ADP.
Activation of human platelet phospholipase C by ionophore A23187 is totally dependent upon cyclo-oxygenase products and ADP.
复制标题
离子载体 A23187 对人血小板磷脂酶 C 的激活完全依赖于环加氧酶产物和 ADP。
DOI：
10.1042/bj2220103
复制
发表时间：
1984
期刊：
影响因子：
--
通讯作者：
S. Rittenhouse
中科院分区：
文献类型：
--
作者：
S. Rittenhouse
暴露于Ca 2+离子载体A23187的人血小板从释放的花生四烯酸中形成环氧合酶代谢物，并分泌致密颗粒取代基，例如ADP。我以前已经证明，A23187引起磷脂酶A2的激活和磷脂酶C的一些刺激。我现在报告，在凝血酶的情况下，激活磷脂酶C响应离子载体是完全依赖于环加氧酶产物的形成和ADP的存在。向人血小板中加入A23187可诱导4，5-二磷酸磷脂酰肌醇含量的短暂下降、磷脂酰肌醇含量的减少以及二酰甘油和磷脂酸的形成。此外，还产生溶血磷脂酰肌醇和游离花生四烯酸。环加氧酶抑制剂或去除ADP的药物的存在部分地削弱了这些变化。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激活磷脂酶C。这种刺激被ADP的竞争者部分抑制。我的结论是磷脂酶C是不激活的钙在血小板中，并建议刺激是完全依赖于受体偶联事件。
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.