Studies on the mechanism of inhibition of hepatic cAMP accumulation by vasopressin

Abstract

Vasopressin elicited a dose-dependent inhibition of glucagon-induced cAMP accumulation in isolated hepatocytes. This response was not diminished by incubation of cells with the calmodulin antagonists trifluoperazine or chlorpromazine and was only slightly reduced in Ca²⁺-depleted hepatocytes. Half-maximal inhibition of cAMP accumulation occurred at 8 × 10^-11 M vasopressin, a dose which does not increase cytosolic Ca²⁺ in hepatocytes. Direct activation of adenylate cyclase by forskolin was significantly inhibited by vasopressin in Ca²⁺-depleted cells. It is concluded that inhibition of hormone-induced cAMP accumulation by vasopressin in liver is not dependent on cellular Ca²⁺ mobilisation but may involve direct inhibition of adenylate cyclase.