POSTRECEPTOR EVENTS ASSOCIATED WITH THROMBIN-INDUCED PLATELET ACTIVATION

Thrombin is by far the most potent platelet agonist. potentially this reflects multiple intracellular processes involved in transmitting the activation signal from the initial contact with a receptor, or bindin g site, to the final platelet response. Platelet membranes have two pu tative receptors: the high affinity glycoprotein Ib, whose function re mains to be clarified, and the moderate affinity autoproteolytic recep tor. The autoproteolytic receptor is a member of a family of receptors , with seven transmembrane domains, which interact with GTP-binding pr oteins. Distal to the membrane, several forms of phospholipase C are a ctivated and roles for both heterotrimeric and low molecular mass GTP- binding proteins have been presented. Phospholipase C acts on inositol phospholipids to generate inositol trisphosphate and diacylglycerol, both of which function as second messengers in thrombin-induced platel et activation. Inositol trisphosphate mobilizes internal calcium store s and this is accompanied, and enhanced, by an influx of calcium from the external milieu. Diacylglycerol and calcium both serve to regulate the activity of multiple protein kinases which, in turn, mediate the phosphorylated state of numerous proteins. Phosphorylation can occur o n serine, threonine or tyrosine residues of target proteins and the ph osphorylated state of these proteins determines the final activation o f the platelet.