Inhibitory action of guanosine 3′,5′-monophosphate on thrombin-induced phosphatidylinositol turnover and protein phosphorylation in human platelets

Human platelets activated by thrombin rapidly produce diglyceride from phosphatidylinositol (PI). Concomitantly, a protein having a molecular weight of about 40,000 is heavily phosphorylated and serotonin is released. These reactions are inhibited in parallel manners by sodium nitroprusside which elevates cyclic GMP. 8-Bromocyclic GMP also inhibits the reactions. Instead, both agents stimulate the phosphorylation of a distinct protein having a molecular weight of about 50,000. Since stimulants of platelets such as thrombin normally increase cyclic GMP, the results imply that this cyclic nucleotide may be involved in a circuit leading to the feedback inhibition of PI hydrolysis presumably through protein phosphorylation.