Vasopressin inhibition of human platelet adenylate cyclase: variable responsiveness between donors and involvement of a G-protein different from Gi

There is controversy concerning the inhibitory effect of arginine-vasopressin (AVP) on human platelet adenylate cyclase activity, which putatively involves Gi as the G-protein. To clarify this point, the effects of AVP on human platelet membranes were studied by measuring the activities of the high-affinity GTPase, as an index of G-protein involvement, and of adenylate cyclase. AVP stimulated GTPase activity in a dose-dependent fashion (KAct = 1.1 +/- 0.2 nM) and caused a parallel adenylate cyclase inhibition (KAct = 1.3 +/- 0.7 nM). The extent of these AVP-induced responses varied considerably from one subject to another but they were linearly related, suggesting a causal relationship between the two activities. Moreover, a difference in responsiveness to the inhibitory effects to epinephrine on adenylate cyclase was also observed between donors. Since the AVP- and epinephrine-stimulated GTPase activities were additive at their respective maximal effect, and in view of the lack of linear relationship between AVP- and epinephrine-induced adenylate cyclase inhibition, our results suggest, that in spite of the AVP inhibitory action on platelet adenylate cyclase, the G-protein involved in this effect is different from Gi.