Effects of Somatostatin on the Hepatic Adenylate Cyclase System in the Rat

Abstract

The effects of somatostatin (SRIF) on the adenylate cyclase system in rat liver and myocardial membranes and porcine renal cortical membranes were studied. SRIF at 1 .mu.g/ml or less did not alter hepatic adenylate cyclase activity (ACA). At higher concentrations, SRIF significantly inhibited basal, NaF and glucagon-stimulated ACA by 5-8 (SRIF-10 .mu.g/ml) and 20-25 (SRIF-100 .mu.g/ml)%. SRIF inhibition of hormone-stimulated hepatic ACA occurred at all concentrations of glucagon. Similar inhibitory effects of SRIF (100 .mu.g/ml) on ACA were also observed in rat myocardial sarcolemma and partially purified porcine renal cortical membranes. Studies of the mechanism(s) whereby SRIF affects hepatic cyclic nucleotide metabolism indicated no alteration in [125I]iodoglucagon binding to liver membranes at concentrations of SRIF which significantly inhibited ACA. Similarly, SRIF was without effect on hepatic phosphodiesterase activity. SRIF at concentrations known to alter pancreatic endocrine function do not affect hepatic adenylate cyclase activity. Pharmacological concentrations of SRIF inhibit hepatic adenylate cyclase activity by a mechanisms independent of hormone binding or phosphodiesterase activation. These results are most compatible with the premise that SRIF''s hypoglycemic potential is mediated via inhibition of pancreatic glucagon secretion.