Two types of hormone-responsive adenylate cyclase in the rat liver.

We have demonstrated the existence of two types of hormone-responsive adenylate cyclase in the isolated perfused rat liver. One, less abundant, is linked to glycogenolysis and the other is not. Glucagon stimulates mainly the glycogenolysis-linked fraction and, to a lesser extent, the fraction which is not linked to glycogenolysis. The suppressive effect of insulin is specific for the glucagon-responsive adenylate cyclase and is inhibited by 3-isobutyl-1-methylxanthine (IBMX). However, this mechanism can explain only partly the ability of insulin to suppress glycogenolysis, and is not observed when cAMP is increased sufficiently by glucagon. Secretin-responsive adenylate cyclase is not linked to glycogenolysis and is suppressed specifically by oxymetazoline. The capacity of this suppressive effect is large and not inhibited by IBMX. These results suggest that there is a functional compartmentalization of cAMP within the hepatocyte or among hepatocytes.