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.
D000067956:Adenylyl Cyclase Inhibitors; D000527:Alprostadil / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000494:pharmacology; D001792:Blood Platelets / Q000201:enzymology*; D002462:Cell Membrane / Q000201:enzymology; D004837:Epinephrine / Q000494:pharmacology; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D010761:Phosphorus Radioisotopes; D014667:Vasopressins / Q000037:antagonists & inhibitors*
D000067956:Adenylyl Cyclase Inhibitors; D010761:Phosphorus Radioisotopes; D014667:Vasopressins; D001127:Arginine Vasopressin; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D000527:Alprostadil; D004837:Epinephrine