Relationship between phosphorylation of blood platelet proteins and secretion of platelet granule constituents II. Effects of different inhibitors

Abstract

The increased phosphorylation of platelet polypeptides in the mol. wt. range 48,000 to 40,000 (P48-40) caused by exposure of intact platelets to collagen fibres was inhibited by concentrations of tetracaine, verapamil, indomethacin, N-ethylmaleimide, cytochalasin B, N 6, 2′-0-dibutyryl cyclic AMP or prostaglandin E 1 that also inhibited the release of platelet 5-hydroxytryptamine by collagen. The smaller increase in phosphorylation of polypeptides in the mol. wt. range 25,000 to 19,000 (P25-19) induced by collagen was also shown to be inhibited by these drugs with the apparent exceptions of prostaglandin E 1 and cytochalasin B. In the former case this was because prostaglandin E 1 itself significantly increased phosphorylation of one or more polypeptides contained in P25-19. The results support previous evidence of a close functional relationship between the increased phosphorylation of specific platelet polypeptides and the secretion of platelet granule constituents and suggest a possible difference in the mechanisms responsible for the inhibitory actions of N 6, 2′-0-dibutyryl cyclic AMP and prostaglandin E 1.