title: Binding characteristics of 3H-dihydroalprenolol to beta-adrenoceptors of rat heart treated with neuraminidase.
abstract: Binding characteristics of the beta-blockers and beta-agonists with the beta-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 beta-adrenoceptors was increased. These data suggest that the binding of the test compounds with the beta-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 beta-antagonists or agonists is: dl-propranolol greater than oxprenolol greater than alprenolol greater than pindolol greater than YM-09538 greater than labetalol greater than acebutolol greater than atenolol greater than metoprolol greater than sotalol greater than butoxamine greater than practolol as antagonists or l-isoproterenol greater than l-epinephrine greater than l-norepinephrine as agonists. A good correlation (r = 0.91, P less than 0.001) was observed between the Ki 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 beta-adrenergic receptor antagonists or agonists.
mesh_terms: D000526:Alprenolol / Q000031:analogs & derivatives*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004082:Dihydroalprenolol / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009439:Neuraminidase / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012794:Sialic Acids / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D011943:Receptors, Adrenergic, beta; D012794:Sialic Acids; D004082:Dihydroalprenolol; D000526:Alprenolol; D009439:Neuraminidase