Discrepancy between inotropic response and cyclic AMP production induced by isoprenaline and forskolin in rat ventricle strips

Abstract

The effects of isoprenaline and forskolin were studied on contractile response and cyclic AMP levels in the right ventricle strips of the rat heart. Isoprenaline, in concentrations ranging from 10 nM to 1 microM, significantly increased, in a concentration-dependent manner, the contractile force in this preparation. Forskolin (1-10 microM), which directly stimulates adenylate cyclase, also produced a concentration-dependent increase in cardiac contractility. The mean EC50 (microM) for the contractile action of isoprenaline was 0.08 +/- 0.014 and that of forskolin 7.3 +/- 1.1 being about 70 times less potent than isoprenaline. However, isoprenaline (0.1 microM) and forskolin (8 microM), which produced about the same inotropic response, increased tissue cyclic AMP levels by about two and five fold respectively, when compared to the basal value. These figures further indicate that while the intracellular levels of cyclic AMP in rat ventricular myocardium may be an important determinant of positive inotropism, the connection between the two parameters is more complex than the simple ratio between the tension generated and the amount of cyclic AMP found inside the cells.