The beta-adrenergic receptors

Herz. 2002 Nov;27(7):683-90. doi: 10.1007/s00059-002-2434-z.


Background: The beta-adrenergic receptors of the myocardium play an important role in the regulation of heart function. The beta-adrenergic receptors belong to the family of G-protein coupled receptors. Three subtypes have been distinguished (beta1-, beta2-, and beta3-adrenoceptors). The receptors consist of seven membrane-spanning domains, three intra- and three extracellular loops, one extracellular N-terminal domain, and one intracellular C-terminal tail.

Pathophysiology: Stimulation of beta-adrenergic receptors by catecholamines is realized via the beta-adrenoceptor-adenylylcyclase-protein kinase A cascade. The second messenger is the cyclic AMP (cAMP). Stimulation of the cascade caused an accumulation of the second messenger cAMP and activated via the cAMP the cAMP dependent protein kinase A (PKA) The PKA phosphorylated, beside other cell proteins, the beta-adrenergic receptors. A phosphorylation of the beta-adrenergic receptors caused - with exception of the beta3-adrenoceptor - an uncoupling and desensitisation of the receptors. Phosphorylation via the G-protein receptor kinase (GRK or betaARK) also caused uncoupling and reduced the beta-adrenergic responsiveness. The uncoupling of the receptor is the prerequisite for receptor internalisation. In the process of internalisation the receptor shifted from the sarcolemma membrane into cytosolic compartments. Chronic beta-adrenergic stimulation caused a down-regulation of the receptors. During this process of desensitisation the expression of the receptor on mRNA and protein level is reduced.

Changing of the receptors in the failing heart: In patients with dilated cardiomyopathy the beta-adrenergic responsiveness of the myocardium is diminished. It was shown that in these patients the expression of the beta1-adrenergic receptor is reduced on the mRNA and protein level. In these patients the expression of the inhibitory G-protein G(i) is increased. Furthermore, the expression of the G-protein receptor kinase is elevated. This kinase induces the uncoupling of the beta-adrenergic receptors. These alterations of the beta-adrenoceptor signal cascade may be induced by an elevated catecholamine release or by agonist-like autoantibodies directed against the beta1-adrenergic receptor found in patients with dilated cardiomyopathy. Both, permanent stimulation with catecholamines and chronic treatment with agonistic anti-beta1-adrenoceptor autoantibodies cause a reduction of the expression of the beta1-adrenoceptor on mRNA and protein level in "in vitro" experiments. Moreover, an over-expression of the beta1-adrenoceptor, the stimulatory G(s) protein, and the protein kinase A induce detrimental alterations of the cardiac function and morphology in transgenic animals. These animals developed heart failure accompanied by an increased mortality rate.

Publication types

  • Review

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use
  • Animals
  • Animals, Newborn
  • Arrhythmias, Cardiac / etiology
  • Autoantibodies / immunology
  • Calcium / metabolism
  • Cardiomyopathy, Dilated / drug therapy
  • Cardiomyopathy, Dilated / metabolism
  • Cardiomyopathy, Dilated / physiopathology*
  • Cell Differentiation
  • Cells, Cultured
  • Down-Regulation
  • Embryo, Mammalian / cytology
  • Heart Failure / etiology
  • Homeostasis
  • Humans
  • Immunoglobulin G / immunology
  • Mice
  • Mice, Transgenic
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / metabolism
  • Phosphorylation
  • Propranolol / therapeutic use
  • RNA, Messenger / genetics
  • Rats
  • Receptors, Adrenergic, beta / genetics
  • Receptors, Adrenergic, beta / immunology
  • Receptors, Adrenergic, beta / metabolism
  • Receptors, Adrenergic, beta / physiology*
  • Receptors, Adrenergic, beta-1 / genetics
  • Receptors, Adrenergic, beta-1 / immunology
  • Receptors, Adrenergic, beta-1 / physiology
  • Sarcolemma / metabolism
  • Signal Transduction
  • Stem Cells
  • Stroke Volume


  • Adrenergic beta-Antagonists
  • Autoantibodies
  • Immunoglobulin G
  • RNA, Messenger
  • Receptors, Adrenergic, beta
  • Receptors, Adrenergic, beta-1
  • Propranolol
  • Calcium