Evidence that cyclic GMP may regulate cyclic AMP metabolism in the isolated frog ventricle

Abstract

Both acetylcholine and 8-bromo cyclic GMP depress the contractile response of the isolated frog ventricle. An investigation has been made of the effects of both substances on the metabolism of endogenous 3,5 cyclic nucleotides. The levels of adenosine 3′, 5′ cyclic monophosphate (cyclic AMP) and guanosine 3′, 5′ cyclic monophosphate (cyclic GMP) were measured after superfusing preparations with varying concentrations (10 −10 to 10 −4 m) of acetylcholine and 8-bromo cyclic GMP. The decline in contractile force was found to be accompanied by a progressive fall in intracellular cyclic AMP and a rise in cyclic GMP levels. Both the decline in contractility and the reduction in endogenous cyclic AMP are attenuated by 10 −4 theophylline. The decline in isometric twitch tension was paralleled, under all conditions, by a quantitatively equivalent reduction in the ratio cyclic AMP: cyclic GMP. The possibility that endogenous cyclic GMP may accelerate the conversion of cyclic AMP to 5 AMP, by stimulating a cyclic GMP-sensitive form of cyclic AMP phosphodiesterase, is discussed.