In Vitro Effects of Beta-2 Agonists on Skeletal Muscle Differentiation, Hypertrophy, and Atrophy

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 10-6 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.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).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.