Functional beta3-adrenoceptor in the human heart

J Clin Invest. 1996 Jul 15;98(2):556-62. doi: 10.1172/JCI118823.


Beta3-adrenoceptors are involved in metabolism, gut relaxation, and vascular vasodilation. However, their existence and role in the human heart have not been documented. We investigated the effects of several beta-adrenoceptor agonists and antagonists on the mechanical properties of ventricular endomyocardial biopsies. In the presence of nadolol, a beta1- and beta2-adrenoceptor antagonist, isoprenaline produced consistent negative inotropic effects. Similar negative inotropic effects also resulted from the action of beta3-adrenoceptor agonists with an order of potency: BRL 37344 > SR 58611 approximately CL 316243 > CGP 12177. The dose-response curve to BRL 37344-decreasing myocardial contractility was not modified by pretreatment with nadolol, but was shifted to the right by bupranolol, a nonselective beta-adrenoceptor antagonist. Beta3-adrenoceptor agonists also induced a reduction in the amplitude and an acceleration in the repolarization phase of the human action potential. Beta3-adrenoceptor transcripts were detected in human ventricle by a polymerase chain reaction assay. These results indicate that: (a) beta3-adrenoceptors are present and functional in the human heart; and (b) these receptors are responsible for the unexpected negative inotropic effects of catecholamines and may be involved in pathophysiological mechanisms leading to heart failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Adrenergic beta-Agonists / pharmacology*
  • Adrenergic beta-Antagonists / pharmacology
  • Base Sequence
  • Biopsy
  • DNA Primers
  • Female
  • Heart / drug effects*
  • Heart / physiology
  • Heart / physiopathology
  • Heart Transplantation
  • Heart Ventricles
  • Humans
  • In Vitro Techniques
  • Isoproterenol / pharmacology
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Myocardial Contraction / drug effects*
  • Myocardium / metabolism
  • Myocardium / pathology
  • Nadolol / pharmacology
  • Polymerase Chain Reaction
  • Receptors, Adrenergic, beta / biosynthesis
  • Receptors, Adrenergic, beta / drug effects
  • Receptors, Adrenergic, beta / physiology*
  • Receptors, Adrenergic, beta-3
  • Structure-Activity Relationship
  • Virulence Factors, Bordetella / pharmacology


  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • DNA Primers
  • Receptors, Adrenergic, beta
  • Receptors, Adrenergic, beta-3
  • Virulence Factors, Bordetella
  • Nadolol
  • Isoproterenol