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

  • Muscle Physiology
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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 p70S6K 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 p70S6K was markedly inhibited by wortmannin, a PI3K inhibitor, and rapamycin, a specific inhibitor of mTOR, suggesting a critical involvement of the PI3K–mTOR-p70S6K 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.

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Abbreviations

mTOR:

Mammalian target of rapamycin

p70S6K :

p70S6 kinase

4E-BP1:

4E-binding protein 1

eIF-4E:

Eukaryotic initiation factor 4E

AR:

Adrenoceptor

PI3K:

Phosphoinositol 3-kinase

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

GPCR:

G protein-coupled receptors

PTX:

Pertussis toxin

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Acknowledgments

We wish to thank Drs. M.L. Marciano, F. Tramontin, and A. Di Pascale for valuable assistance at different times in some of the experiments.

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Authors and Affiliations

  1. Department of Experimental Pharmacology, University of Naples Federico II, via D. Montesano, 49 80131, Naples, Italy

    Maria Concetta Miniaci, Mariarosaria Bucci, Rita Santamaria, Carlo Irace, Anna Cantalupo, Giuseppe Cirino & Pietro Scotto

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  1. Maria Concetta Miniaci
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  2. Mariarosaria Bucci
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Correspondence to Pietro Scotto.

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Miniaci, M.C., Bucci, M., Santamaria, R. et al. CL316,243, a selective β3-adrenoceptor agonist, activates protein translation through mTOR/p70S6K signaling pathway in rat skeletal muscle cells. Pflugers Arch - Eur J Physiol 465, 509–516 (2013). https://doi.org/10.1007/s00424-012-1213-9

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