Action potential shortening through the putative beta4-adrenoceptor in ferret ventricle: comparison with beta1- and beta2-adrenoceptor-mediated effects

Br J Pharmacol. 1998 Aug;124(7):1341-4. doi: 10.1038/sj.bjp.0702013.

Abstract

The electrophysiological responses to (-)-CGP 12177 ((-)-4-(3-tertiarybutylamino-2-hydroxypropoxy) benzimidazol-2-one), an agonist for the putative beta4-adrenoceptor, were investigated on isolated perfused ferret hearts paced at 100 min(-1) and compared to those of (-)-noradrenaline and (-)-adrenaline, mediated through beta1- and beta2-adrenoceptors respectively. The three agonists decreased ventricular monophasic action potential duration but prolonged the action potential plateau; beta3-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 beta1- and putative beta4-adrenoceptors may be different.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects*
  • Adrenergic beta-Agonists / pharmacology*
  • Animals
  • Epinephrine / pharmacology
  • Female
  • Ferrets
  • Heart Ventricles / drug effects*
  • Male
  • Norepinephrine / pharmacology
  • Propanolamines / pharmacology*
  • Receptors, Adrenergic, beta / classification
  • Receptors, Adrenergic, beta / drug effects*
  • Ventricular Function

Substances

  • Adrenergic beta-Agonists
  • Propanolamines
  • Receptors, Adrenergic, beta
  • CGP 12177
  • Norepinephrine
  • Epinephrine