title: Coexistence of functioning beta 1- and beta 2-adrenoceptors in single myocytes from human ventricle.
abstract: BACKGROUND
  Both beta 1- and beta 2-adrenoceptors (beta 1 AR and beta 2 AR) are present in human ventricle. This study was designed to determine whether the two subtypes contribute to contraction in single myocytes from human heart.
  
  
  RESULTS
  (-)-Epinephrine increased the contraction amplitude and velocity of single myocytes isolated from the ventricles of failing and nonfailing human hearts. Concentration-response curves to (-)-epinephrine were constructed in the presence and absence of selective antagonists for beta 1 AR (CGP 20712A) and beta 2 AR (ICI 118,551). Responses to (-)-epinephrine were antagonized to a variable degree by the blockers, suggesting heterogeneous contribution of beta 1AR and beta 2AR among cells. The most common response in single myocytes was that ICI 118,551 (50 nmol/L) shifted the concentration-response curve less than 10-fold: this was lower than the 100-fold shift expected for a pure beta 2AR effect. Inclusion of CGP 20712A (300 nmol/L) with ICI 118,551 shifted the (-)-epinephrine curve still further. These observations suggest that both beta 1AR and beta 2AR contribute to the increase in contraction amplitude with (-)-epinephrine in this group of myocytes. When 300 nmol/L CGP 20712A was present as the sole antagonist, only a marginal shift of the concentration-response curve for (-)-epinephrine was usually observed, indicating that beta 1AR were not mediating the effect of these low concentrations of (-)-epinephrine. Both beta 1AR and beta 2AR mediated a considerable abbreviation of the time to peak contraction and time to 50% relaxation in the single cells.
  
  
  CONCLUSIONS
  beta 1AR and beta 2AR coexist and function on human ventricular myocytes. At low (-)-epinephrine concentrations, contractile responses are predominantly mediated by beta 2AR rather than beta 1AR in myocytes from failing hearts.
authors.affiliation: Department of Cardiac Medicine, National Heart and Lung Institute, London, England, UK.
authors.forename: F
authors.initials: F
authors.lastname: del Monte
authors.forename: A J
authors.initials: AJ
authors.lastname: Kaumann
authors.forename: P A
authors.initials: PA
authors.lastname: Poole-Wilson
authors.forename: D G
authors.initials: DG
authors.lastname: Wynne
authors.forename: J
authors.initials: J
authors.lastname: Pepper
authors.forename: S E
authors.initials: SE
authors.lastname: Harding
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D004837:Epinephrine / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000737:chemistry / Q000166:cytology*; D011412:Propanolamines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000187:drug effects / Q000502:physiology*
chemical_list: D000319:Adrenergic beta-Antagonists; D007093:Imidazoles; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551; C049763:CGP 20712A; D004837:Epinephrine