Signal Transduction in Blood Platelets: Regulation of Adenylate Cyclase and Phospholipase C

Abstract

Cells including platelets respond to many agonists through signal transduction mechanisms in the plasma membrane composed of specific receptors, guanine nucleotide-binding proteins (G proteins) and effector enzymes, which synthesize molecules that function as intracellular 'second messengers'. One of these enzymes, adenylate cyclase, which is subject to positive and negative regulation by different agonists, generates cyclic AMP (cAMP) that inhibits platelet responses. A second enzyme, phospholipase C, is stimulated by many agonists that induce platelet aggregation and secretion and generates diacylglycerol (DG) and inositol phosphates (including IP2 and IP3). DG activates protein kinase C (PKG), which has both stimulatory and inhibitory effects on platelet responses, whereas IP3 mobilizes Ga ions from intracellular stores, thereby stimulating many Ca2+ dependent reactions involved in platelet activation. In this thesis, the effects of agonists that stimulate platelets, particularly platelet-activating factor (PAF), on platelet adenylate cyclase and phospholipase C activities have been studied with a view of defining some of the biochemical properties and interactions of these signal transduction pathways.