CL316,243, a selective β₃-adrenoceptor agonist, activates protein translation through mTOR/p70S6K signaling pathway in rat skeletal muscle cells

Functional β₃-adrenoceptors have been found in skeletal muscle where they mediate metabolic oxidation and glucose utilization. Whether β₃-adrenoceptors (ARs) also play any role in muscle protein metabolism still remains uncertain. By using rat L6 myocyte cultures, we found that CL316,243, a β₃-AR selective agonist, at the concentration of 10^-6 M for 24 h, induced a significant increase of skeletal muscle constitutive proteins such as H- and L-myosin and β-actin. Such effect was correlated to an increased expression of phosphorylated p70^S6K that was significantly inhibited by β₃-AR antagonist, SR 59230A, but not by β₂-AR antagonist, ICI-118,551. The CL316,243-induced activation of p70^S6K was markedly inhibited by wortmannin, a PI3K inhibitor, and rapamycin, a specific inhibitor of mTOR, suggesting a critical involvement of the PI3K-mTOR-p70^S6K signaling cascade in the anabolic response of L6 cells to β₃-AR agonist. Taken together, these results suggest that stimulation of β₃-AR in skeletal muscle cells activates a specific signaling pathway leading to protein synthesis and, eventually, muscle growth.