title: Regulation of contractility and metabolic signaling by the β2-adrenergic receptor in rat ventricular muscle.
abstract: OBJECTIVE
  Cardiac function is modulated by the sympathetic nervous system through β-adrenergic receptor (β-AR) activity and this represents the main regulatory mechanism for cardiac performance. To date, however, the metabolic and molecular responses to β(2)-agonists are not well characterized. Therefore, we studied the inotropic effect and signaling response to selective β(2)-AR activation by tulobuterol.
  
  
  METHODS
  Strips of rat right ventricle were electrically stimulated (1Hz) in standard Tyrode solution (95% O(2), 5% CO(2)) in the presence of the β(1)-antagonist CGP-20712A (1μM). A cumulative dose-response curve for tulobuterol (0.1-10μM), in the presence or absence of the phosphodiesterase (PDE) inhibitor IBMX (30μM), or 10min incubation (1μM) with the β(2)-agonist tulobuterol was performed.
  
  
  RESULTS
  β(2)-AR stimulation induced a positive inotropic effect (maximal effect=33±3.3%) and a decrease in the time required for half relaxation (from 45±0.6 to 31±1.8ms, -30%, p<0.001) after the inhibition of PDEs. After 10min of β(2)-AR stimulation, p-AMPKα(T172) (54%), p-PKB(T308) (38%), p-AS160(T642) (46%) and p-CREB(S133) (63%) increased, without any change in p-PKA(T197).
  
  
  CONCLUSIONS
  These results suggest that the regulation of ventricular contractility is not the primary function of the β(2)-AR. Rather, β(2)-AR could function to activate PKB and AMPK signaling, thereby modulating muscle mass and energetic metabolism of rat ventricular muscle.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Murcia, Murcia, Spain. j.perezschindler@unibas.ch
authors.forename: Joaquín
authors.initials: J
authors.lastname: Pérez-Schindler
authors.forename: Andrew
authors.initials: A
authors.lastname: Philp
authors.forename: Keith
authors.initials: K
authors.lastname: Baar
authors.forename: Jesús
authors.initials: J
authors.lastname: Hernández-Cascales
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000502:physiology; D058672:Adrenergic beta-2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D058672:Adrenergic beta-2 Receptor Antagonists; D018343:Receptors, Adrenergic, beta-2; D055372:AMP-Activated Protein Kinases