Effects of exogenous neurotransmitters on contractility and cyclic nucleotide metabolism in the isolated frog ventricle

Abstract

A study has been made of the effecis of acctylcholine and adrenaline on the metabolism of 3'.5'-cyclic nucleotides by the isolated frog ventricle. Measurements of adenosine 3'.5'-cyclic mono-phosphate (cyclic AMP) and guanosine 3'.5'-cyclic monophosphate (cyclic GMP) were made: (a) at various times during responses produced by a given concn of acetylcholine (10 −7 M) or adrenaline (10 −6 M): and (b) at fixed times following exposure to different concns of the two agonists. The negative inotropic effect of acctylcholine is accompanied by reciprocal changes in the two cyclic nucleotides: cyclic GMP levels rise and cyclic AMP falls. Both effects are dose-related. A more complex pattern of changes occurs during responses produced by adrenaline. The initial increase in twitch tension is accompanied by a transient reduction in cyclic GMP and by a large increase in cyclic AMP. The rate at which cvclic AMP accumulates is greatest at the time when cyclic GMP levels are maximally depressed. An increase in cyclic GMP. seen later, coincides with a gradual fall in both twitch tension and cyclic AMP. The increments in both cyclic AMP and cyclic GMP. measured when the twitch is maximally potentiated, arc dose-related. The magnitude of the decrease in peak twitch tension produced by acetvlcholine and of the increase produced by adrenaline correlate closely with corresponding changes in the relative proportion of cyclic AMP: cyclic GMP present in the fibres. The possible significance ol the changes in cyclic AMP and cyclic GMP in modulating the response of the ventricle is discussed.