CL316,243, a Selective β3‐Adrenoceptor Agonist Activates Protein Synthesis Through mTOR/p70S6K Signaling Pathway in L6 Cells.

Abstract

The existence of β3‐adrenergic receptors (AR) in skeletal muscle has been demonstrated by the detection of the β3‐mRNA and protein and by the selective effects β3‐AR agonists on metabolic oxidation and glucose utilization. However, the role of β3‐AR on protein metabolism in skeletal muscle remains still unclear. To determine whether β3‐AR regulates protein translation we evaluated in L6 skeletal muscle cells the effect of CL316,243, a selective β3‐AR agonist, on the rate of protein synthesis and on the activation of the Akt/mTOR/ p70S6K signaling pathway which is known to support the protein synthesis requirement during muscle growth. When L6 cells were incubated in the presence of CL 316,243, we observed a net increase of [35S] methionine incorporation into muscle cell proteins such myosin heavy chain and myosin light chain at 24 hr. The anabolic effect of CL 316,243 was associated with an increase of p70S6K which was inhibited by the β3‐AR antagonist, SR 59230A, but not by the β2‐AR antagonist ICI 118551. In addition, the increase in p70S6K levels induced by CL 316,243 was inhibited by wortmannin, a PI3K inhibitor, and by rapamycin, mTOR inhibitor suggesting that β3‐AR regulates protein synthesis via PI3K/Akt/ p70S6K signaling pathway. This finding unveils a new cellular mechanism by which β‐AR system exerts anabolic actions on skeletal protein metabolism and therefore regulates skeletal muscle mass.