Inotropic responses of the frog ventricle to adenosine triphosphate and related changes in endogenous cyclic nucleotides.

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Abstract
The response of the isolated frog ventricle to treatment with exogenous ATP was studied. Measurements of membrane potential, isometric twitch tension and levels of endogenous 3'',5''-cyclic nucleotides were made at various times during the ATP-induced response. The inotropic effects of ATP are accompanied by changes in the shape of the action potential; these effects are dose related. ATP has a potent stimulatory effect on the metabolism of endogenous 3'',5''-cyclic nucleotides. ATP exerts a dual effect on the ventricle and the contractile response is regulated by changes in the metabolism of 3'',5%-cyclic nucleotides. The effects of idomethacin indicate a possible involvement of prostaglandins in mediating the ATP response. The initial effect of ATP on the ventricle apparently is to increase the permeability of the fibers to Ca2+. The relationship between 3'',5'' cyclic nucleotide levels and ventricular contractility is discussed. The antagonistic effects of 3'',5''-cyclic AMP and 3'',5''-cyclic GMP are expressed at the level of certain phosphoproteins which regulate the availability of Ca2+ and the sensitivity of the contractile proteins to Ca2+.