PHOSHOINOSITTIDE METABOLISM AND PLATELET SECRETION

正常情况下，人类的血小板是主要的参与者 在病理生理学上，在凝血和血栓形成中，可以影响 血管组织的收缩反应。血小板也有助于 动脉斑块的形成。血小板的激活依赖于 血小板保存过程中钙离子的动员和分泌 颗粒。受刺激的血小板表现出非常迅速和显著的变化 在磷脂酰肌醇代谢之前，钙动员和分泌。 越来越多的证据表明，磷脂酰肌醇(PtdIns， PtdIns4，5P-2)通过磷脂酶C(PLC)引起钙离子的动员 通过肌醇三磷酸(IP-3)，并通过 二酰甘油(DG)，促进血小板形态变化。 释放的花生四烯酸转化为前列腺素代谢物可以 也参与到这样的PLC激活中来。 利用毛细管气相色谱、电泳法、薄层析等技术 层析、离子交换和高压液相色谱，以及 高压膜通透性，所有这些都是在我们的 在实验室，我们将回答以下问题： 1)PLC是如何调节的？2)PLC对磷脂酰肌醇的作用 (PtdIns)依赖于PtdIns4，5P-2的水解性 IP-3在血小板中的作用？4)肾上腺素增强作用吗？ 前列腺素相关的磷脂酰肌醇代谢？5)为什么凝血酶a 更有效的花生四烯酸释放激动剂 前列腺素H-2/血栓素A-2类似物U46619？ 澄清影响因素(及其作用机制) 肌醇磷脂周转及其协同激活作用的研究 肾上腺素作用下的血小板应能增强我们对事件的理解 控制正常和病理状态下的血小板功能。

The human platelet is a major participant, normally and pathophysiologically, in coagulation and thrombosis, and can affect the contractile response of vascular tissue. Platelets also contribute to the formation of arterial plaques. Activation of platelet is dependent upon Ca-2-+ mobilization and secretion of material in platelet storage granules. Stimulated platelets display very rapid and marked alterations in phosphoinositide metabolism prior to Ca-2-+ mobilization and secretion. Increasing evidence indicate that breakdown of phosphoinositides (PtdIns, PtdIns4,5P-2) by phospholipase C (PLC) causes the mobilization of Ca-2-+ via myoinositol trisphosphate (IP-3), and activation of kinase by diacylglycerol (DG), which promote platelet morphological changes. Conversic of released arachidonic acid to prostaglandin metabolites can also participate in such activation of PLC. Utilizing techniques of capillary gas chromatography, electrophoresis, thin layer, ion exchange, and high pressure liquid chromatographies, as well as high voltage membrane permeabilization, all routinely performed in our laboratory, we will address the following questions: 1) How is PLC regulated? 2) Is the action of PLC on phosphatidylinositol (PtdIns) dependent upon hydrolysis of PtdIns4,5P-2? 3) What is the function of IP-3 in platelets? 4) Does epinephrine potentiate prostaglandin-related phosphoinositide metabolism? 5) Why is thrombin a more effective agonist for arachidonic acid release than is the prostaglandin H-2/thromboxane A-2 analogue U46619? Clarification of the factors (and their mechanisms of action) that affect phosphoinositide turnover and elucidation of the synergistic activation of platelets by epinephrine should enhance our understanding of events controlling platelet function in normal and pathological states.