β₁- and β₂-adrenergic receptor stimulation differ in their effects on PGC-1α and atrogin-1/MAFbx gene expression in...

Adrenaline changes expression of the genes encoding peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α), which is known as a regulator of muscle size, and atrogin-1/muscle atrophy F-box (MAFbx), which is a muscle-specific ubiquitin ligase. However, the subtype of β-adrenergic receptor (β-AR) involved in regulating these genes in skeletal muscle is not yet well defined. In this study, the effects of intraperitoneal injection of adrenaline and three β_1-3-AR selective agonists on chick skeletal muscle metabolism were examined, to evaluate the functions of β-AR subtypes. Adrenaline decreased atrogin-1/MAFbx mRNA levels accompanied by an increase in PGC-1α mRNA and protein levels. However, among the three selective agonists, only the β₁-AR agonist, dobutamine, increased PGC-1α mRNA and protein levels, while the β₂-AR agonist, clenbuterol, suppressed atrogin-1/MAFbx mRNA levels. In addition, preinjection of the β₁-AR antagonist, acebutolol, and the β₂-AR antagonist, butoxamine, inhibited the adrenaline-induced increase in PGC-1α mRNA levels and the decrease in atrogin-1/MAFbx mRNA levels, respectively. Compared with adrenaline administration, the β₃-AR agonist, BRL37344, decreased PGC-1α mRNA levels and increased atrogin-1/MAFbx mRNA levels. These results suggest that, in chick skeletal muscle, PGC-1α is induced via the β₁-AR, while atrogin-1/MAFbx is suppressed via the β₂-AR.