Effects of uridine triphosphate on contractility, cyclic nucleotide levels and membrane potential in the isolated frog ventricle

Abstract

A study has been made of the effects of uridine 5'-triphosphate (UTP) on the isolated frog ventricle. Preparations were superfused with solutions containing different concentrations of UTP, and changes in contractility, cyclic nucleotide levels and membrane potential were measured. UTP produced a long lasting increase in isometric twitch tension, which was unaffected by adrenergic receptor antagonists (propranolol and phentolamine). The levels of adenosine 3',5'-cyclic monophosphate (cyclic AMP) and guanosine 3',5'-cyclic monophosphate (cyclic GMP) were measured at different times during exposure of the ventricle to 10(-4) M UTP. The increase in the force of contraction was found to be accompanied by a rise in intracellular cyclic AMP. Cyclic GMP levels were seen to fall initially, but then to increase later, as both twitch and cyclic AMP started to decline. UTP also produced marked changes in the shape of the action potential; its duration and positive overshoot were both increased. The effects of UTP on twitch tension, cyclic nucleotide levels and action potential parameters were all dose-related. The change in contractility was found to be linearly related to (a) the ratio of the amount of cyclic AMP: cyclic GMP present in the fibres, and (b) to the increase in duration of the action potential. These results suggest that cyclic AMP, cyclic GMP and the availability of Ca2+ may all be involved in mediating the response to UTP.