Apparent lack of beta 2 adrenergic receptors in porcine myocardium.
The aim of this study was to investigate the relative numbers of myocardial beta 1 and beta 2 receptors in pigs. Membrane particles from left ventricular porcine and mixed ventricular rat myocardium were examined for subtypes of beta adrenergic receptors with a radioligand binding technique using [125I]-cyanopindolol (ICYP) as trace, and the new highly beta 1 selective antagonist Sandoz 204 545 and the beta 2 selective antagonist ICI 118 551 for displacement. Radioligand displacement experiments were also performed using propranolol, isoprenaline and terbutaline. The displacement curves obtained with the subtype selective antagonists and agonist revealed biphasic inhibition of specific ICYP binding in rat preparations, indicating a beta 1/beta 2 ratio of approximately 2/1. In porcine preparations displacement of specific ICYP binding with all agents resulted in monophasic curves, thus sharply contrasting the rat preparations. Affinity constants of displacing drugs derived from these monophasic curves indicated that the specific binding site was a beta 1 receptor. No displacement compatible with beta 2 affinity was found. In the same rat preparations we found that adenylate cyclase activation and inhibition by beta receptor subtype specific agonists and antagonists were mediated by two receptor subtypes, whereas in the pig, adenylate cyclase activation and its inhibition seemed to occur via only one receptor subtype, the beta 1 adrenoceptor.
Bjørnerheim
R
R
Department of Medicine B, Rikshospitalet University Hospital, Oslo, Norway.
Golf
S
S
Hansson
V
V
D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000378:metabolism / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D004789:Enzyme Activation / Q000187:drug effects; D006352:Heart Ventricles; D009206:Myocardium / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000032:analysis* / Q000145:classification / Q000172:deficiency; D013552:Swine / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D000262:Adenylyl Cyclases