Action potential shortening through the putative β4‐adrenoceptor in ferret ventricle: comparison with β1‐ and β2‐adrenoceptor‐mediated effects

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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.British Journal of Pharmacology (1998) 124, 1341–1344; doi:10.1038/sj.bjp.0702013