Abstract
The electrophysiological responses to (−)-CGP 12177 ((−)-4-(3-tertiarybutylamino-2-hydroxypropoxy) benzimidazol-2-one), an agonist for the putative β4-adrenoceptor, were investigated on isolated perfused ferret hearts paced at 100 min−1 and compared to those of (−)-noradrenaline and (−)-adrenaline, mediated through β1- and β2-adrenoceptors respectively. The three agonists decreased ventricular monophasic action potential duration but prolonged the action potential plateau; β3-adrenoceptor-selective agonists had no effect. (−)-CGP 12177 was the most potent, but (−)-noradrenaline the most efficacious; both agonists caused ventricular extra-systoles. Because only (−)-noradrenaline but not (−)-CGP 12177 elicited shortening of the refractory period, the mechanism of arrhythmias mediated through β1- and putative β4-adrenoceptors may be different.
Keywords: Ferret heart; action potentials; β1-, β2- β3- and putative β4-adrenoceptors; arrhythmias; ventricular pressure; (−)-noradrenaline, (−)-adrenaline and (−)-CGP 12177
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