Effects of exogenous neurotransmitters on contractility and cyclic nucleotide metabolism in the isolated frog ventricle.
A study has been made of the effects of acetylcholine and adrenaline on the metabolism of 3',5'-cyclic nucleotides by the isolated frog ventricle. Measurements of adenosine 3',5'-cyclic monophosphate (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 acetylcholine 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 cyclic 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, are dose-related. The magnitude of the decrease in peak twitch tension produced by acetylcholine 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 of the changes in cyclic AMP and cyclic GMP in modulating the response of the ventricle is discussed.
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D011896:Rana temporaria; D016276:Ventricular Function
D000242:Cyclic AMP; D006152:Cyclic GMP; D000109:Acetylcholine; D004837:Epinephrine