Characterization of mechanical effects and beta-adrenoceptor binding of prenalterol in rat myocardium.

The partial beta-agonist prenalterol has been found to differ from the full agonist isoprenaline in some aspects of its cardiac action. We therefore studied in rat myocardium whether prenalterol elicited the same qualitative changes of the contraction-relaxation cycle as was previously found for isoprenaline. We also measured binding of prenalterol to beta-adrenoceptors. Prenalterol augmented relaxation more than contraction and thus evoked the same qualitative changes of the contraction-relaxation cycle as did isoprenaline. However, the response developed slower than that to isoprenaline, and the effect on relaxation followed a more protracted time course than the effect on contraction. Prenalterol bound non-selectively to beta 1- and beta 2-adrenoceptors in both heart and lung broken cell preparations. pKd for binding to beta-adrenoceptors and pD2 values for functional effects in heart were similar, i.e. prenalterol had to occupy half the amount of beta-adrenoceptors in order to evoke half-maximal functional effects. The non-selective alpha-blocker phentolamine potentiated the effects of prenalterol on contraction, but did not change the equilibrium binding of prenalterol to cardiac beta-adrenoceptors. Phentolamine did not change the potency and efficacy of isoprenaline. Thus, although prenalterol qualitatively evoked the same response as isoprenaline, it also exhibited some properties which differed.