Effects of a beta-adrenergic agonist on protein turnover in muscle cells in culture.
beta-Adrenergic agents powerfully stimulate muscle growth in animals. Whether the mechanism of action involves a direct effect on muscle cell beta-receptors or is secondarily due to a beta-induced alteration in the hormonal environment is not known. To assess whether direct beta-receptor activation results in muscle protein accretion, we examined the effect of the beta-agonist zinterol on several anabolic processes in L8 muscle cells in culture. In vivo feeding of zinterol (26.5 ppm) to rats significantly increased muscle weight by 15%. In vitro, zinterol stimulated lactate release from L8 cells whereas propranolol inhibited this process, demonstrating that these cells have functional beta-receptors both before and after fusion. We measured several anabolic processes, in both serum-stimulated and quiescent cells, over a wide range of zinterol concentrations. Zinterol had no effect on protein or DNA synthesis, protein degradation, or rates of amino acid uptake. These data suggest that the in vivo muscle growth stimulation is either indirect or some in vivo requirements (e.g. tension and nerve interactions) are necessary for expression of the effect.
McElligott
M A
MA
Merck Sharp & Dohme Research Laboratories, Department of Animal Drug Discovery, Rahway, NJ 07065.
Chaung
L Y
LY
Barreto
A
A
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000375:Aging; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D004983:Ethanolamines / Q000494:pharmacology*; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D008297:Male; D024510:Muscle Development; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D014176:Protein Biosynthesis; D051381:Rats; D012016:Reference Values; D013936:Thymidine / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D000596:Amino Acids; D004983:Ethanolamines; D007773:Lactates; C002904:zinterol; D013936:Thymidine