Similarities Between Effects of Adenosine 3′,5′-Monophosphate and Guanosine 3′,5′-Monophosphate on Liver and Adrenal Metabolism

Abstract

The 3′,5′-monophosphates of adenosine (cyclic AMP) and guanosine (cyclic GMP) both produced glucagon-Hke responses when added to a perfusate recirculating through isolated rat livers. They stimulated hepatic glucose output, glycogenolysis, lactate uptake and urea production, and the induction of tyrosine aminotransferase. Enhanced glycogenolysis was associated with increased activity of phosphorylase and lowered activity of the active form of UDPglucose-glycogen transferase. The effects of either nucleotide were quantitatively similar at equimolar concentrations, and when given in combination in submaximally stimulating amounts they additively increased hepatic glucose output. Since the effects of cyclic GMP were obtained in the absence of any change in tissue levels of cyclic AMP, it is unlikely that they were secondary to alterations in cyclic AMP metabolism. In rat adrenal quarters, cyclic AMP and cyclic GMP stimulated steroidogenesis similarly to ACTH. The dose responses of steroidogenesis to the nucleotides were similar, with cyclic GMP being at least as effective as equimolar amounts of cyclic AMP. 6-N,2′-O-dibutyryl cyclic AMP produced similar changes in glucose mobilization, glycogenolysis, and the activities of phosphorylase and UDPglucose-glycogen transferase in liver, and steroidogenesis in adrenal tissue. It was, however, approximately 100-fold more effective on a molar basis than either cyclic AMP or cyclic GMP. These findings raise the possibility that cyclic GMP may also be a “second messenger” in hormone action. (Endocrinology85: 711, 1969)