Adenosine depresses contractility and stimulates 3′,5′ cyclic nucleotide metabolism in the isolated frog ventricle

Abstract

Adenosine depresses the contractile response of the isolated frog ventricle. An investigation has been made of its effects on the metabolism of endogenous 3′,5′ cyclic nucleotides. The levels of adenosine 3′,5′ cyclic monophosphate (3′,5′ cyclic AMP) and guanosine 3′,5′ cyclic monophosphate (3′,5′ cyclic GMP) were measured at different times during exposure of the ventricle to adenosine (10 −3 m). The decline in isometric twitch tension is found to be accompanied by a progressive fall in intracellular 3′,5′ cyclic AMP and a concomitant rise in 3′,5′ cyclic GMP. These effects are dose related. It is suggested that the ability of adenosine to stimulate 3′,5′ cyclic nucleotide turnover is the result of a fall in intracellular Ca 2+, acting via the Ca 2+-binding protein modulator, calmodulin. Interestingly, the extent to which the contractile response is depressed is found to be paralleled closely by a quantitatively equivalent reduction in the ratio 3′,5′ cyclic AMP: 3′,5′ cyclic GMP. A possible biochemical basis for the antagonistic regulatory effects of 3′,5′ cyclic AMP and 3′,5′ cyclic GMP on ventricular contractility, implied by these (and other) results, is discussed briefly.