Interaction of stable prostaglandin endoperoxide analogs U46619 and U44069 with human platelet membranes: Coupling of receptors with high-affinity GTPase and adenylate cyclase

Abstract It has been demonstrated using a membrane preparation of human platelets that stable analogs of PGH 2 , U46619 and U44069, control the activity of adenylate cyclase and a high-affinity hormone-sensitive GTPase. At 10 -8 -10 -6 M, the analogs inhibit the basal activity of adenylate cyclase by 20–25%. With a further rise in U46619 and U44069 concentrations up to 10 -5 -10 -4 M, the inhibition is abolished and adenylate cyclase activity is stimulated in a dose-dependent fashion. In the presence of PGE 1 , only inhibitory action of U46619 was observed at all the concentrations tested. The inhibitory action of the analogs on adenylate cyclase correlates with the activation of the high-affinity hormone-sensitive GTPase. It is concluded that U46619 and U44069 inhibit human platelet adenylate cyclase via specific receptors coupled to the GTP-binding inhibitory protein.