Activation of epinephrine-sensitive adenylate cyclase in rat liver by cytosolic protein-nucleotide complex.

The cytosolic fraction from rat liver enhanced the basal and glucagon-sensitive adenylate cyclase (EC 4.6.1.1) of hepatic plasma membranes and revealed its (R)-(-)-epinephrine sensitivity. Such phenomena were usually obtained by the addition of low concentrations of GTP to the medium employed for the cyclase assay. Comparative studies of the behavior of the cytosolic factor and GTP in response to various treatments were performed. We present evidence that the stimulatory activity of the soluble factor was reduced after treatment by alkaline phosphatase, by the nucleotide phosphohydrolases present in the plasma membranes, and by trypsin. These results strongly suggest that the soluble activator is a nucleotide-protein complex and further demonstrate that GTP may be of physiological significance in the regulation of the adenylate cyclase system.