β-Adrenergic Receptors Subtypes in Myocardium

  • P. Robberecht
  • P. Chatelain
Part of the Update in Intensive Care and Emergency Medicine book series (UICM, volume 6)


β-adrenergic receptors have been classified into 2 subtypes based on differences in the specificity of action of natural catecholamines [1]. For β1-adrenergic receptors, epinephrine and norepinephrine were about equivalent. In contrase, for β2-adrenergic receptors, epinephrine was considerably more potent than norepinephrine. This initial classification had survived to the screening of a large number of synthetic agonists and antagonists of increasing selectivity, and 20 years after Land’s publication, it is still obvious that only 2 subtypes of β-adrenergic receptors are present in mammalian tissues. Until the last 8 years, β1- and β2-adrenergic receptors were essentially distinguished one from the other by pharmacological studies based on the relative efficiency of selected molecules: Among the most studied are the β1-selective antagonists practolol, metoprolol and atenolol, the β2-selective agonist zinterol and the β2 selective antagonist ICI 118551. More recently, efforts have been made to distinguish the receptors on the basis of chemical and/or immunological differences [2], but it is only very recently that the complete amino-acid sequence of both β1- and β2-adrenergic receptors had definitively established that β1- and β2-adrenergic receptors were distinct chemical entities. However, the two pharmacologically distinct β1- and β2-adrenergic receptors can be found in a single tissue, subserving sometimes distinct functions, and in some cases both subtypes have been found in the same cell [3].


Adrenergic Receptor Positive Inotropic Effect Calcium Entry Blocker Adenylate Cyclase System Adrenergic Receptor Subtype 
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  1. 1.
    Lands AM, Arnold DA, McAuliff A, Ludena JP, Brown TG (1967) Differentiation of receptors systems activated by sympathomimetic amines. Nature 214: 597–598PubMedCrossRefGoogle Scholar
  2. 2.
    Venter JC, Fraser CM, Harrison LC (1980) Autoantibodies to beta 2-adrenergic receptors: a possible cause of adrenergic hyporesponsiveness in allergic rhinitis and asthma. Science 207: 1361–1363PubMedGoogle Scholar
  3. 3.
    Homburger V, Lucas M, Rosenbaum E, Vassent G, Bockaert J (1981) Presence of both beta-1 and beta-2 adrenergic receptors in cat and guinea-pig heart. Mol Pharmacol 29: 463–469Google Scholar
  4. 4.
    Stiles GL, Strasser RH, Caron MG, Lefkowitz RJ (1983) Mammalian beta-adrenergic receptors. Structural differences in beta-1 and beta-2 subtypes reveal by peptide maps. J Bio Chem 258: 10689–10694Google Scholar
  5. 5.
    Stiles GL, Benovic JL, Caron MG, Lefkowitz RJ (1984) Mammalian beta-adrenergic receptors. Distinct glycoprotein populations containing high mannose of complex type carbohydrate chains. J Biol Chem 259: 8655–8663PubMedGoogle Scholar
  6. 6.
    Dixon RAF, Kobilka BK, Strader DJ, et al (1986) Cloning of the gene and CDNA for mammalian beta-adrenergic receptors and homology with rhodopsin. Nature 321: 75–79PubMedCrossRefGoogle Scholar
  7. 7.
    Frielle T, Collins S, Daniel KW, Caron MG, Lefkowitz RJ, Kobilka BH (1987). Cloning of the DNA for the human p7-adrenergic receptor. Proc Natl Acad Sci 84: 7920–7924PubMedCrossRefGoogle Scholar
  8. 8.
    Strader CD, Candelore MR, Rands E, Dixon RAF (1987) Beta-adrenergic receptor subtype is an intrinsic property of the receptor gene product. Mol Pharmacol 32: 179–183PubMedGoogle Scholar
  9. 9.
    Masu Y, Nokayama K, Tamaki H, Harada Y, Kuno M, Nakanishi S (1987) CNDA cloning of bovine substance-K receptor through ocyte expression system. Nature 329: 836–838PubMedCrossRefGoogle Scholar
  10. 10.
    Hargrave PA, McDowell JH, Curtis DR, et al (1983) Structure of bovine rhodopsin. Biophys Struct Mech 9: 235–244PubMedCrossRefGoogle Scholar
  11. 11.
    Lefkowitz RJ, Benovic JC, Kobilka B, Caron MG (1986) Beta-adrenergic receptors and rhodopsin: shedding new light on an ould subject. Trends Pharmacol Sci 7: 444–448CrossRefGoogle Scholar
  12. 12.
    Kerlavage AR, Fraser CM, Venter JC (1987) Muscarinic cholinergic receptors structure: molecular biological support for subtypes. Trends Pharmacol Sci 8: 426–431CrossRefGoogle Scholar
  13. 13.
    Buck SH, Pruss RM, Krstenansky JC, Robinson PJ, Stauderman KA (1988) A tachykinin peptide receptor joins on elite club. Trends Pharmacol Sci 9: 3–5PubMedCrossRefGoogle Scholar
  14. 14.
    Dohlman HG, Bouvier M, Benovic JC, Caron MG, Lefkowitz RJ (1987) The multiple membrane spanning topography of the beta-2 adrenergic receptor. Localization of the sites of binding glycosylation and regulatory phosphorylation by limited proteolysis. J Biol Chem 262: 14282–14288PubMedGoogle Scholar
  15. 15.
    Minneman KP, Hegstrand LR, Molinoff PB (1979) Simultaneous determination of beta-1 and beta-2 adrenergic receptors in tissue containing both receptors subtypes. Mol Pharmacol 16: 34–46PubMedGoogle Scholar
  16. 16.
    Minneman KP, Hedberg A, Molinoff PB (1979) Comparison of beta-adrenergic receptors subtypes in mammalian tissues. J Pharmacol Exp Ther 211: 502–508PubMedGoogle Scholar
  17. 17.
    Hancock AA, De Lean AL, Lefkowitz RJ (1979) Quantitative resolution of beta-adrenergic receptors subtypes by selective ligand binding: application of a computerized model fitting technique. Mol Pharmacol 16: 1–9PubMedGoogle Scholar
  18. 18.
    Brodde OE, Leifert FJ, Krehl HJ (1982) Coexistence of beta 1- and beta 2-adrenoceptors in the rabbit heart: quantitative analysis of the regional distribution by (—)3H dihydroalprenolol binding. J Cardiovasc Pharmacol 4: 34–43PubMedCrossRefGoogle Scholar
  19. 19.
    Rugg EL, Barnett DB, Nahorski SR (1978) Coexistence of beta 1- and beta 1-adrenoceptors in mammalian lung: evidence from direct binding studies. Mol Pharmacol 14: 996–1005PubMedGoogle Scholar
  20. 20.
    Kent RS, De Lean A, Lefkowitz RJ (1980) Quantitative analysis of beta-adrenergic receptor interactions: resolution of high and low affinity states of the receptor by computer modeling of ligand binding data. Mol Pharmacol 17: 14–23PubMedGoogle Scholar
  21. 21.
    Hedberg A, Minneman KP, Molinoff PB (1980) Differential distribution of beta-1 and beta-2 adrenergic receptors in rat and guinea-pig heart. J Pharmacol Exp Ther 212: 503–508PubMedGoogle Scholar
  22. 22.
    Juberg EN, Minneman KP, Abel PW (1985) Beta 1- and beta 2-adrenoceptor binding and functional response in right and left atria of rat heart. Naunyn-Schmiedeberg’s Arch Pharmacol 330: 193–202PubMedCrossRefGoogle Scholar
  23. 23.
    Buxton IL, Brunton LL (1985) Direct analysis of beta-adrenergic receptors subtypes on intact adult ventricular myocytes of the rat. Circ Res 56: 126–132PubMedGoogle Scholar
  24. 24.
    Brodde OE, Beckeringh JJ, Michel MC (1987) Human heart beta-adrenoceptors: a fair comparison with lymphocyte beta-adrenoceptors? Trends in Pharmacol Sci 8: 403–407CrossRefGoogle Scholar
  25. 25.
    Stiles GI, Taylor S, Lefkowitz RJ (1983) Human cardiac beta-adrenergic receptors: subtype heterogeneity delineated by direct radioligand binding. Life Sci 33: 467–473PubMedCrossRefGoogle Scholar
  26. 26.
    Robberecht P, Delhaye M, Taton G, et al (1983) The human heart beta-adrenergic receptors: I. Heterogeneity of the binding sites: presence of 50% beta 1- and 50% beta 2-adrenergic receptors. Mol Pharmacol 24: 169–173PubMedGoogle Scholar
  27. 27.
    Hedberg A, Kempf F, Josephson ME, Molinoff PB (1985) Coexistence of beta-1 and beta-2 adrenergic receptors in the human heart: effects of treatment with receptor antagonists of calcium entry blockers. J Pharmacol Exp Therap 234: 561–568Google Scholar
  28. 28.
    Freyss-Beguin M, Griffaton G, Lechat P, et al (1983) Comparison of the chronotropic effect and the cyclic AMP accumulation induced by beta 2-agonists in rat heart cell culture. Br J Pharmacol 78: 717–723PubMedGoogle Scholar
  29. 29.
    Kaumann AJ (1986) The beta 1-adrenoceptor antagonist CGP 20712 An unmasks beta 2adrenoceptors activated by (—) adrenaline in rat sinoatrial node. Naunyn-Schmiedeberg’s Arch Pharmacol 332: 406–409PubMedCrossRefGoogle Scholar
  30. 30.
    Liang BT, Frame LH, Molinoff PB (1985) Beta 2-adrenergic receptors contribute to catecholamine-stimulated shortening of action potential duration in dog atrial muscle. Proc Natl Acad Sci, USA 82: 4521–4525PubMedCrossRefGoogle Scholar
  31. 31.
    Brodde OE, O’Hara N, Zerkowski HR, Rohm N (1984) Human cardiac beta-adrenoceptors: both beta 1-and beta 2-adrenoceptors are functionnaly coupled to the adenylate cyclase in right atrium. J Cardiovasc Pharmacol 6: 1184–1191PubMedGoogle Scholar
  32. 32.
    Waelbroeck M, Taton G, Delhaye M, et al (1983) The human heart beta-adrenergic receptors: II. Coupling of beta 2-adrenergic receptors with the adenylate cyclase system. Mol Pharmacol 24: 174–182PubMedGoogle Scholar
  33. 33.
    Gille E, Lemoine H, Ehle B, Kaumann AJ (1985) The affinity of (—) propanolol for beta land beta 2-adrenoceptors of human heart. Differential antagonism of the positive inotropic effects and adenylate cyclase stimulation by (—) noradrenaline and (—) adrenaline. Naunyn-Schmiedeberg’s Arch Pharmacol 331: 60–70CrossRefGoogle Scholar
  34. 34.
    Kaumann AJ, Lemoine H (1987) Beta 2-adrenoceptor mediated positive inotropic effect of adrenaline in human ventricular myocardium. Quantitative discrepencies with binding and adenylate cyclase stimulation. Naunyn-Schmiedeberg’s Arch Pharmacol 335: 403–411CrossRefGoogle Scholar
  35. 35.
    Zerkowski HR, Ikezono K, Rohm N, Reidemeister JC, Brodde OE (1986) Human myocardial beta-adrenoceptors: demonstration of both beta 1- and beta 2-adrenoceptors mediating contractile response to beta-agonists on the isolated right atrium. Naunyn-Schmiedeberg’s Arch Pharmcol 332: 142–147CrossRefGoogle Scholar
  36. 36.
    Brown JE, Mc Leod AA, Shand DG (1986) In support of cardiac chronotropic beta 2adrenoceptors. Am J Cardiol 57: 11F - 16FPubMedCrossRefGoogle Scholar
  37. 37.
    Brown JE, Mc Leod AA, Shand DG (1983) Evidence for cardiac beta 2-adrenoceptors in man. Clin Pharmacol Ther 33: 424–428PubMedCrossRefGoogle Scholar
  38. 38.
    Bristow MR, Ginsberg R, Umans V, et al (1986) Beta 1- and beta 2-adrenergic receptor subpopulations in non-failing and failing human ventricular myocardium: coupling of both receptors subtypes to muscle contraction and selective beta 1-receptor down-regulation in heart failure. Circ Res 59: 297–309PubMedGoogle Scholar
  39. 39.
    Lefkowitz RJ (1981) Clinical physiology of adrenergic receptor regulation. Am J Physiol 243: E43 - E47Google Scholar
  40. 40.
    Limas C, Limas CJ (1978) Reduced number of beta-adrenergic receptors in the myocardium of spontaneously hypertensive rats. Biochem Biophys Res Com 83: 710–714PubMedCrossRefGoogle Scholar
  41. 41.
    Robberecht P, Winand J, Chatelain P, et al (1981) Comparison of beta-adrenergic receptors and the adenylate cyclase system with muscarinic receptors and guanylate cyclase activities in the heart of spontaneously hypertensive rats. Biochem Pharmacol 30: 385–387PubMedCrossRefGoogle Scholar
  42. 42.
    Chatelain P, Wolfe BB, Molinoff PB (1982) In “Hypertensive Mechanisms. The spontaneously hypertensive rat as a model to study human hypertension” Racher, Clough, Ganten (eds), Schattauer, Stuttgart New York, pp 454–457Google Scholar
  43. 43.
    Yamada S, Ishima T, Tornita T, Hayashi M, Okada T, Hayashi E (1984) Alterations in cardiac alpha and beta-adrenoceptors during the development of spontaneous hypertension. J Pharmac Exp Ther 228: 454–460Google Scholar
  44. 44.
    Brodde OE, Schuler S, Kretsch R, et al (1986) Regional distribution of ß-adrenoceptors in both atria and ventricles in severe congestive cardiomyopathy. J Cardiovasc Pharmacol 8: 1235–1242PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1988

Authors and Affiliations

  • P. Robberecht
  • P. Chatelain

There are no affiliations available

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