ACTION-POTENTIAL SHORTENING THROUGH THE PUTATIVE BETA(4)-ADRENOCEPTORIN FERRET VENTRICLE - COMPARISON WITH BETA(1)-ADRENOCEPTOR-MEDIATED AND BETA(2)-ADRENOCEPTOR-MEDIATED EFFECTS

The electrophysiological responses to (-)-CGP 12177 ((-)-4-(3-tertiary butylamino-2-hydroxypropoxy) benzimidazol-2-one), an agonist for the p utative beta(4)-adrenoceptor, were investigated on isolated perfused f erret hearts paced at 100 min(-1) and compared to those of (-)-noradre naline and (-)-adrenaline, mediated through beta(1)- and beta(2)-adren oceptors respectively. The three agonists decreased ventricular monoph asic action potential duration but prolonged the action potential plat eau; beta(3)-adrenoceptor-selective agonists had no effect. (-)-CGP 12 177 was the most potent, but (-)-noradrenaline the most efficacious; b oth agonists caused ventricular extra-systoles. Because only (-)-norad renaline but not (-)CGP 12177 elicited shortening of the refractory pe riod, the mechanism of arrhythmias mediated through beta(1)- and putat ive beta(4)-adrenoceptors may be different.