PHOSHOINOSITTIDE METABOLISM AND PLATELET SECRETION

人类血小板是一个主要的参与者，通常， 在病理生理学上，在凝血和血栓形成中，并且可以影响 血管组织的收缩反应。 同时，也有助于 动脉斑块的形成。 血小板的活化依赖于 血小板贮存过程中Ca ~（2+）的动员和物质的分泌 颗粒。 刺激血小板显示非常迅速和显著的变化 在钙离子动员和分泌之前磷酸肌醇代谢。 越来越多的证据表明，磷酸肌醇（PtdIns， PtdIns 4，5 P-2）引起Ca-2+的动员 通过三磷酸肌醇（IP-3），以及通过 甘油二酯（DG），促进血小板形态学变化。 释放的花生四烯酸转化为前列腺素代谢物， 也参与这种PLC的激活。 利用毛细管气相色谱、电泳、薄层色谱等技术 层、离子交换和高压液相色谱，以及 高压膜透化，所有常规进行，在我们的 实验室，我们将解决以下问题： 1)PLC是如何管理的？ 2)PLC对磷脂酰肌醇的作用 （PtdIns）依赖于PtdIns 4，5 P-2？ 3)是什么 IP-3在血小板中的作用 4)肾上腺素会增强 三尖杉定相关的磷酸肌醇代谢？ 5)为什么凝血酶是 更有效的花生四烯酸释放的激动剂， 前列腺素H-2/血栓素A-2类似物U46619？ 澄清影响环境的因素（及其作用机制） 磷酸肌醇周转和阐明的协同激活 通过肾上腺素刺激血小板应该能增强我们对 在正常和病理状态下控制血小板功能。

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.