Receptor-Effector Coupling in Platelets: Roles of Guanine Nucleotides

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Abstract
Platelet aggregation and degranulation are complex cellular responses initiated by interaction of physiological stimuli with specific plasma membrane receptors. Two immediate effects of the activation of stimulatory platelet receptors have been well documented» namely inhibition of adenylate cyclase1–3 and the cleavage of membrane phosphoinositides to diacylglycerol and inositol phosphates by phospholipase C.3,4 Initial attempts1 at correlating the inhibition of adenylate cyclase with platelet aggregation failed when it was found that although some aggregating agents (e.g. ADP) inhibited adenylate cyclase in intact platelets, others (e.g. vasopressin) did not.2 Moreover, it eventually became clear that inhibition of this enzyme serves only to reduce the inhibition of platelet aggregation by agents that increase platelet cyclic AMP levels, such as PGE1.6 In contrast, evidence that increases in intracellular Ca2+ free could activate platelets3 and that phosphoinositide breakdown was closely associated with Ca2+ mobilization in platelets and other cells,7,8 led to the concept that it is the receptor-mediated activation of phospholipase C that generates the signals leading to platelet aggregation and de-granulation. 9,10

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