Rao G H
Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis 55455.
Indian J Physiol Pharmacol. 1993 Oct;37(4):263-75.
Blood platelets interact with a variety of soluble agonists such as epinephrine and adenosine diphosphate (ADP); many insoluble cell matrix components, including collagen and laminin, and biomaterials used for construction of invasive medical devices. These interactions stimulate specific receptors and glycoprotein-rich domains (integrins and nonintegrin) on the plasma membrane and lead to the activation of intracellular effector enzymes. The majority of regulatory events appear to require free calcium. Ionized calcium is the primary bioregulator, and a variety of biochemical mechanisms modulate the level and availability of free cytosolic calcium. Major enzymes that regulate the free calcium levels via second messengers include phospholipase C, phospholipase A2, and phospholipase D, together with adenylyl and guanylyl cyclases. Activation of phospholipase C results in the hydrolysis of phosphatidyl inositol 4,5-bisphosphate and formation of second messengers 1,2-diacylglycerol and inositol 1,4,5-trisphosphate (IP3). Diglyceride induces activation of protein kinase C, whereas IP3 mobilizes calcium from internal membrane stores. Elevation of cytosolic calcium stimulates phospholipase A2 and liberates arachidonic acid. Free arachidonic acid is transformed to a novel metabolite, thromboxane A2, by fatty acid synthetases. Thromboxane A2 is the major metabolite of this pathway and plays a critical role in platelet recruitment, granule mobilization and secretion. Up-regulation in signalling pathways will increase the risk for clinical complications associated with thromboembolic episodes. Down-regulation of signal transduction mechanisms may precipitate bleeding diathesis or stroke.
血小板与多种可溶性激动剂相互作用，如肾上腺素和二磷酸腺苷（ADP）；许多不溶性细胞基质成分，包括胶原蛋白和层粘连蛋白，以及用于构建侵入性医疗器械的生物材料。这些相互作用刺激质膜上的特定受体和富含糖蛋白的结构域（整合素和非整合素），并导致细胞内效应酶的激活。大多数调节事件似乎需要游离钙。离子钙是主要的生物调节因子，多种生化机制调节游离胞质钙的水平和可用性。通过第二信使调节游离钙水平的主要酶包括磷脂酶C、磷脂酶A2和磷脂酶D，以及腺苷酸环化酶和鸟苷酸环化酶。磷脂酶C的激活导致磷脂酰肌醇4,5-二磷酸的水解和第二信使1,2-二酰甘油和肌醇1,4,5-三磷酸（IP3）的形成。二酰甘油诱导蛋白激酶C的激活，而IP3从内膜储存中动员钙。胞质钙的升高刺激磷脂酶A2并释放花生四烯酸。游离花生四烯酸通过脂肪酸合成酶转化为一种新的代谢产物血栓素A2。血栓素A2是该途径的主要代谢产物，在血小板募集、颗粒动员和分泌中起关键作用。信号通路的上调将增加与血栓栓塞事件相关的临床并发症的风险。信号转导机制的下调可能导致出血素质或中风。
