title: In vitro effects of Beta-2 agonists on skeletal muscle differentiation, hypertrophy, and atrophy.
abstract: BACKGROUND
  : Beta-2 agonists are widely used in the treatment of asthma and chronic obstructive pulmonary disease for their effect on airway smooth muscle relaxation. They also act on skeletal muscle, although their reported ergogenic effect is controversial.
  
  
  OBJECTIVE
  : To evaluate the in vitro effects of short-acting and long-acting beta-2 agonists on adrenergic receptor (ADR) expression, hypertrophy, and atrophy markers, in a skeletal muscle cell line.
  
  
  METHODS
  : The C2C12 cell line was used as a model of skeletal muscle differentiation. ADR messenger RNA expression was evaluated in proliferating myoblasts, committed cells, and differentiated myotubes, in basal conditions and after treatment with 10 M clenbuterol, salbutamol, salmeterol, and formoterol. Effect of beta-2 agonists on gene and protein expression of hypertrophy and atrophy markers was assessed in differentiated myotubes.
  
  
  RESULTS
  : Our study shows that beta-2 ADR messenger RNA was expressed and progressively increased during cell differentiation. Beta-2 agonist treatment did not affect its expression. Skeletal muscle hypertrophy markers (fast and slow myosin, myogenin) were not modulated by any of the beta-2 agonists evaluated. However, clenbuterol induced a significant, dose-dependent downregulation of skeletal muscle atrophy genes (atrogin-1, MuRF-1, and cathepsin L).
  
  
  CONCLUSIONS
  : The reported ergogenic effect of beta-2 agonists, if any, should be considered as drug-specific and not class-specific and that of clenbuterol is mediated by the inhibition of the atrophic pathway.
authors.affiliation: 1Institute of Translational Pharmacology, National Research Council, Rome, Italy 2Department of Medicine, "Sapienza" University, Rome, Italy 3Department of Health Science, University of Rome 'Foro Italico', Rome, Italy 4Department of Internal Medicine, Endocrinology Unit, University of Tor Vergata, Rome, Italy 5Department of Internal Medicine, Second University of Naples, Naples, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Wannenes
authors.forename: Loretta
authors.initials: L
authors.lastname: Magni
authors.forename: Matteo
authors.initials: M
authors.lastname: Bonini
authors.forename: Ivan
authors.initials: I
authors.lastname: Dimauro
authors.forename: Daniela
authors.initials: D
authors.lastname: Caporossi
authors.forename: Costanzo
authors.initials: C
authors.lastname: Moretti
authors.forename: Sergio
authors.initials: S
authors.lastname: Bonini