INHIBITION OF [³H]‐DIHYDROALPRENOLOL BINDING TO RAT CARDIAC MEMBRANES BY VARIOUS β‐BLOCKING AGENTS

Abstract

Binding of [ 3 H]‐dihydroalprenolol ([ 3 H]‐DHA) to rat cardiac membranes was rapid and reversible (fcj = 0.633‐0.701 × 10 6 M _1 s _1 and fc_ x = 0.0017‐0.0043 s _1 ). [ 3 H]‐DHA bound to a single class of binding sites with an equilibrium dissociation constant (Kd25°c) Of 5.7 ± 1.1 × 10 −9 M. This binding was specific and the order of potency of adrenoceptor agonists in competing for the binding sites was (—)‐isoproterenol < (±)‐isoproterenol < (+)‐isoproterenol < (—)‐adrenaline < (—)‐noradrenaline. This was in agreement with the β 1 nature of the cardiac β‐receptors. Cardioselective β‐blockers (i.e. metoprolol, acebutolol and practolol) were shown to have lower binding site affinities, when compared to other blockers. This may be related to steric hindrance by the side‐chain at the aromatic end of these molecules.