Functional beta3-adrenoceptor in the human heart.
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.
Gauthier
C
C
Laboratoire de Physiopathologie et Pharmacologie Cellulaires et Moléculaires, CHU de Nantes, France.
Tavernier
G
G
Charpentier
F
F
Langin
D
D
Le Marec
H
H
D000200:Action Potentials / Q000187:drug effects; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D001483:Base Sequence; D001706:Biopsy; D017931:DNA Primers; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D016027:Heart Transplantation; D006352:Heart Ventricles; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009248:Nadolol / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011943:Receptors, Adrenergic, beta / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D022702:Receptors, Adrenergic, beta-3; D013329:Structure-Activity Relationship; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D017931:DNA Primers; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; D010566:Virulence Factors, Bordetella; D009248:Nadolol; D007545:Isoproterenol