CL316,243, a selective [beta]^sub 3^-adrenoceptor agonist, activates protein translation through mTOR/p70S6K signaling pathway in rat skeletal muscle cells

• Published in: Pflügers Archiv Vol. 465; no. 4; p. 509
• Main Authors: Miniaci, Maria Concetta, Bucci, Mariarosaria, Santamaria, Rita, Irace, Carlo, Cantalupo, Anna, Cirino, Giuseppe, Scotto, Pietro
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer Nature B.V 01-04-2013
• DOI: 10.1007/s00424-012-1213-9
• EISSN: 1432-2013
• ISSN: 0031-6768

Functional [beta]^sub 3^-adrenoceptors have been found in skeletal muscle where they mediate metabolic oxidation and glucose utilization. Whether [beta]^sub 3^-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 [beta]^sub 3^-AR selective agonist, at the concentration of 10^sup â '6^â[euro][per thousand]M for 24Â h, induced a significant increase of skeletal muscle constitutive proteins such as H- and L-myosin and [beta]-actin. Such effect was correlated to an increased expression of phosphorylated p70^sup S6K^ that was significantly inhibited by [beta]^sub 3^-AR antagonist, SR 59230A, but not by [beta]^sub 2^-AR antagonist, ICI-118,551. The CL316,243-induced activation of p70^sup S6K^ was markedly inhibited by wortmannin, a PI3K inhibitor, and rapamycin, a specific inhibitor of mTOR, suggesting a critical involvement of the PI3Kâ[euro]"mTOR-p70^sup S6K^ signaling cascade in the anabolic response of L6 cells to [beta]^sub 3^-AR agonist. Taken together, these results suggest that stimulation of [beta]^sub 3^-AR in skeletal muscle cells activates a specific signaling pathway leading to protein synthesis and, eventually, muscle growth.[PUBLICATION ABSTRACT]