Cardiovascular Drugs and Therapy

, Volume 13, Issue 2, pp 123–126 | Cite as

Beta-Blocker Selectivity at Cloned Human Beta1- and Beta2-Adrenergic Receptors

  • Carol Smith
  • Milt Teitler


Summary. The ratio between the affinities of beta-blockers for the beta2- and beta1-receptors is often used to predict the cardioselectivity and the potential consequences of blocking beta2-receptor–mediated effects of adrenergic receptor blockers. These ratios have been traditionally determined using various in vitro models of beta2 and beta1-receptor antagonist activity, including isolated organ preparations and redioligand binding in tissues from various species. The data from these studies, while useful, are complicated by the use of different preparations, techniques, and nonhuman models. Recombinant cell lines expressing human beta2 and beta1 receptors have been developed, allowing for the direct comparison of the affinities of the beta-blockers for the beta2 and beta1 receptors under identical conditions, and allowing a precise determination of the beta1-receptor selectivity of the beta-blockers. Bisoprolol, atenolol, propranolol, betaxolol, metoprolol, carvedilol, and ICI 118, 551 were compared for their beta-receptor selectivity using membranes prepared from recombinant cells selectively expressing human beta2 and beta1 receptors. Bisoprolol was found to have the highest selectivity for the beta1 receptor, displaying a beta2//beta1 ratio of 19 (a 19-fold higher affinity for the beta receptor than for the beta2 receptor). Atenolol, metoprolol, and betaxolol displayed lower, although significant, selectivity for the beta1 receptor, whereas propranolol and carvedilol displayed no signiicant beta-adrenergic selectivity. ICI 118,55 was selective for the beta2 receptor. The equilibrium dissociation constants of the beta-blockers for the beta1 and beta2 receptors were generally similar to previously reported values. The affinity ratios were also generally similar to previously reported values.

beta-blocked selectivity cloned beta receptors cardioselectivity 


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  1. 1.
    Cleland JG, Bristow MR, Erdmann E, Remme WJ, Swedberg K, Waagstein F. Beta-blocking agents in heart failure. Should they be used and how? Eur Heart J 1996;17:1629–1639.Google Scholar
  2. 2.
    Dargie HJ. Angina and left ventricular dysfunction. Eur Heart J 1996;17(Suppl G.):2–7.Google Scholar
  3. 3.
    Doughty RN, Sharpe N. Beta-adrenergic blocking agents in the treatment of congestive heart failure: Mechanisms and clinical results Ann Rev Med 1997;48:103–114.Google Scholar
  4. 4.
    Goldstein S. Beta-blockers in hypertensive and coronary heart disease Arch Intern Med 1996;156:–1276.Google Scholar
  5. 5.
    Goldstein S. Beta-blocking drugs and coronary heart disease Cardiovasc Drugs Ther 1997;11(Suppl. 1):219–225.Google Scholar
  6. 6.
    Hampton JR. Choosing the right beta-blocker. A guide to selection Drugs 1994;48:549–568.Google Scholar
  7. 7.
    Hjalmarson A. Empiric therapy with beta-blockers Pacing Clin Electrophysiol 1994;17:460–466.Google Scholar
  8. 8.
    Caron MG, Lefkowitz RJ. Catecholamine receptors: Structure, function, and regulation. Recent Progr Horm Res 1993;48:277–290.Google Scholar
  9. 9.
    Ostrowski J, Kjelsberg MA, Caron MG, Lefkowitz RJ. Mutagenesis of the beta 2-adrenergic receptor: How structure elucidates function Annu Rev Pharmacol Toxicol 1992;32:167–183.Google Scholar
  10. 10.
    Roth NS, Lefkowitz RJ, Caron MG. Structure and function of the adrenergic receptor. Adv Expe Med Biol 1991;308:223–238.Google Scholar
  11. 11.
    Collins S, Lohse MJ, O'Dowd B, Caron MG, Lefkowitz RJ. Structure and regulation of G protein-coupled receptors: The beta 2-adrenergic receptor as a model Vitam Horm 1991;46:1–39.Google Scholar
  12. 12.
    Belvisi M. Beta-blocker induced asthma: A role for sensory nerve hyperresponsiveness Clin Exp Allergy 1996;26:1343–1346.Google Scholar
  13. 13.
    Wellstein A, Palm D, Belz GG. Affinity and selectivity of beta-adrenoceptor antagonists in vitro. J Cardiovasc Pharmacol 1986;8(Suppl. 11):S36–S40.Google Scholar
  14. 14.
    Hjalmarson A, Waagstein F. The role of beta-blockers in the treatment of cardiomyopathy and ischaemic heart failure Drugs 1994;47(Suppl. 4):31–39.Google Scholar
  15. 15.
    Brodde OE. Bisoprolol (EMD 33512), a highly selective beta 1-adrenoceptor antagonist: In vitro and in vivo studies. J Cardiovas Pharmacol 1986;8(Suppl. 11):S29–S35Google Scholar
  16. 16.
    Wellstein A, Palm D, Belz GG. Affinity and selectivity of beta-adrenoceptor antagonists in vitro. J Cardiovasc Pharmacol 1986;8(Suppl. 11):S36–S40.Google Scholar
  17. 17.
    Minneman KP, Pittman RN, Molinoff PB. Beta-adrenergic receptor subtypes: Properties, distribution, and regulation. Annu Revi Neurosci 1981;4:419–461.Google Scholar
  18. 18.
    Frielle T, Caron MG, Lefkowitz RJ. Properties of the beta 1-and beta 2-adrenergic receptor subtypes revealed by molecular cloning Clini Chem 1989;35:721–725.Google Scholar
  19. 19.
    Caron MG, Kobilka BK, Frielle T, et al. Cloning of the cDNA and genes for the hamster and human beta 2-adrenergic receptors. J Receptor Res 1988;8:7–21.Google Scholar
  20. 20.
    Frielle T, Collins S, Daniel KW, Caron MG, Lefkowitz RJ, Kobilka BK. Cloning of the cDNA for the human beta 1-adrenergic receptor. Proc Natl Acad Sci USA 1987;84:7920–7924.Google Scholar
  21. 21.
    Leonhardt S, Gorospe E, Hoffman BJ, Teitler M. Molecular pharmacological differences in the interaction of serotonin with 5-hydroxytryptamine 1 C and 5-hydroxytryptamine 2 receptors. Mol Pharmacol 1992;42:328–335.Google Scholar
  22. 22.
    Minnear FL, DeMichele MA, Leonhardt S, Andersen TT, Teitler M. Isoproterenol antagonizes endothelial permeability induced by thrombin and thrombin receptor peptide. J Appl Physiol 1993;75:1171–1179.Google Scholar

Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • Carol Smith
  • Milt Teitler
    • 1
  1. 1.Department of Pharmacology & ToxicologyAlbany Medical CollegeAlbanyUSA

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