Ligand-independent negative chronotropic responses of rat and mouse right atria to beta-adrenoceptor antagonists.
Negative chronotropic effects of beta-adrenoceptor (betaAR) antagonists on right atria from reserpine-treated rats and mice were determined as a test of their inverse agonist activities. BetaAR antagonist ICI-118,551 and nonselective betaAR antagonists alprenolol, propranolol, and timolol produced negative chronotropic effects. In contrast, nonselective betaAR antagonists pindolol and nadolol as well as beta1AR-selective antagonists atenolol, acebutolol, and metoprolol did not cause a significant decrease in atrial rates. The neutral antagonist pindolol but not the inverse agonist alprenolol inhibited the negative chronotropic activities of ICI-118,551. Isoprenaline, salbutamol, and noradrenaline produced positive chronotropic effects; the chronotropic effects of isoprenaline and salbutamol but not of noradrenaline were antagonized by ICI-118,551. It is concluded that both beta1AR and beta2AR mediate positive chronotropic effects of catecholamines on rat and mouse atria but only beta2AR are constitutively active.
Varma
D R
DR
Department of Pharmacology and Therapeutics, McGill University, Montréal, Canada. dvarma@pharma.mcgill.ca
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000145:classification / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006325:Heart Atria / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D008024:Ligands; D008297:Male; D051379:Mice; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects; D012110:Reserpine / Q000494:pharmacology*
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D008024:Ligands; D018342:Receptors, Adrenergic, beta-1; D012110:Reserpine; D009638:Norepinephrine