Effects of Guanosine 3',5'-Monophosphate on the Perfused Rat Liver

The effect of exogenous guanosine 3',5'-monophosphate (cyclic GMP) and adenosine 3',5'-monophosphate (cyclic AMP) were compared in the isolated rat liver perfused with buffer containing blood cells and albumin. Cyclic GMP was ⠓ to ½ as potent as cyclic AMP in stimulating glucose production, net glycogenolysis, glyconeogenesis from lactate, and release of K + . Cyclic GMP activated glycogen phosphorylase and inhibited the incorporation of 14 C from lactate into glycogen. The effectiveness of cyclic GMP in the perfused liver was unexpected in view of its relatively weak ability to mimic cyclic AMP in broken cell preparations. Cyclic GMP did not act by raising the tissue level of cyclic AMP nor did it promote the release of cyclic AMP into the medium as did glucagon or epinephrine. Cyclic GMP was observed to accumulate in the liver to a much greater extent than cyclic AMP, and this probably accounts for its unexpected potency. The two nucleotides were removed by the liver at similar rates. Insulin inhibited the effects of submaximal concentrations of cyclic AMP on hepatic glycogenolysis, but did not alter the effects of cyclic GMP.