BINDING CHARACTERISTICS OF ³H-DIHYDROALPRENOLOL TO β-ADRENOCEPTORS OF RAT HEART TREATED WITH NEURAMINIDASE

Abstract

Binding characteristics of the β-blockers and β-agonists with the β-adrenoceptors were investigated in ³H-dihydroalprenolol (³H-DHA) binding to rat heart membranes treated with neuraminidase. When 60% of the total sialic acid content in the membranes was removed, reproducibility of the binding assay became much better than was attainable without neuraminidase treatment, and the maximum density of β-adrenoceptors was increased. These data suggest that the binding of the test compounds with the β-adrenergic receptors in cardiac muscle was under the influence of the sialic acid of the glycocalyx of the membrane. The ³H-DHA binding sites in membranes treated with neuraminidase showed a strict stereo-specificity when tested with propranolol. The ranking order of inhibition of β-antagonists or agonists is: dl-propranolol > oxprenolol > alprenolol > pindolol > YM-09538 > labetalol > acebutolol > atenolol > metoprolol > sotalol > butoxamine > practolol as antagonists or l-isoproterenol > I-epinephrine > I-norepinephrine as agonists. A good correlation (r=0.91, P < 0.001) was observed between the K; values observed by the present binding assay and the pA₂ observed in the guinea-pig atria relative to the positive inotropic effect by Bieth et al. (Br. J. Pharmacol. 68, 563-569, 1980), indicating that the present method will be useful for screening new β-adrenergic receptor antagonists or agonists.