Action potential shortening through the putative beta4-adrenoceptor in ferret ventricle: comparison with beta1- and beta2-adrenoceptor-mediated effects.
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.
Department of Biochemistry, University of Cambridge, UK.
M D
MD
Lowe
A A
AA
Grace
J I
JI
Vandenberg
A J
AJ
Kaumann
D000200:Action Potentials / Q000187:drug effects*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D005289:Ferrets; D006352:Heart Ventricles / Q000187:drug effects*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000145:classification / Q000187:drug effects*; D016276:Ventricular Function
D000318:Adrenergic beta-Agonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C033394:CGP 12177; D009638:Norepinephrine; D004837:Epinephrine