title: CL316,243, a selective β3-adrenoceptor agonist, activates protein translation through mTOR/p70S6K signaling pathway in rat skeletal muscle cells.
abstract: 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.
authors: Department of Experimental Pharmacology, University of Naples Federico II, via D. Montesano, 49 80131, Naples, Italy.
authors: Maria Concetta
authors: MC
authors: Miniaci
authors: Mariarosaria
authors: M
authors: Bucci
authors: Rita
authors: R
authors: Santamaria
authors: Carlo
authors: C
authors: Irace
authors: Anna
authors: A
authors: Cantalupo
authors: Giuseppe
authors: G
authors: Cirino
authors: Pietro
authors: P
authors: Scotto
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D058667:Adrenergic beta-3 Receptor Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004149:Dioxoles / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011412:Propanolamines / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects*; D051381:Rats; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D020123:Sirolimus / Q000494:pharmacology; D024744:Skeletal Muscle Myosins / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000077191:Wortmannin
chemical_list: D000199:Actins; D058667:Adrenergic beta-3 Receptor Agonists; D000319:Adrenergic beta-Antagonists; D000730:Androstadienes; D004149:Dioxoles; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011412:Propanolamines; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D020123:Sirolimus; D024744:Skeletal Muscle Myosins; D058570:TOR Serine-Threonine Kinases; D000077191:Wortmannin; C097869:3-(2-ethylphenoxy)-1-(1,2,3,4-tetrahydronaphth-1-ylamino)-2-propanol oxalate; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; C026777:ICI 118551; C546845:mTOR protein, rat