Mode of action of beta-adrenergic agonists on muscle protein metabolism

Shaoquan Ji, Purdue University

Abstract

Beta-adrenergic agonists ($\beta$-agonists) can induce muscular hypertrophy and are potential lean growth enhancers. The purpose of these experiments was to elucidate the mechanism by which $\beta$-agonists can alter muscle protein metabolism. In a primary muscle cell culture system, a full $\beta$-agonist, isoproterenol, was shown to act directly on myotubes to increase synthesis rates of total, myofibrillar, and cytoplasmic protein pools. Protein degradation rates for these protein pools appear to be unaltered by isoproterenol. An in vivo model in pigs was used to study the interaction between a $\beta\sb1$-agonist, ractopamine, and dietary protein on nitrogen metabolism and gene expression. At higher dietary protein, ractopamine resulted in increased muscling and increased nitrogen retention. At lower dietary protein, ractopamine increased muscling with no effect on nitrogen retention, indicating that ractopamine caused a repartitioning of nitrogen from nonmuscle toward muscle protein pools. Alpha-actin mRNA expression was increased by ractopamine at both high and low dietary protein levels, consistent with increased protein synthesis. Activity of m-calpain was increased by ractopamine, but $\mu$-calpain and calpastatin activities were not affected by ractopamine with increased m-calpain activity, suggesting that ractopamine probably impose no effect on inhibition of muscle protein degradation. Skeletal muscle specific calpain (sm-calpain) mRNA was identified for the first time in swine. Ractopamine repressed sm-calpain mRNA in muscle. Since the substrates for sm-calpain are unknown, the implications of ractopamine inhibition of sm-calpain expression remain unclear. Attempts were also made to identify any other muscle genes that might be down-regulated by ractopamine via differential hybridization. Following a limited number of clones screened, no positive clones were confirmed. In conclusion, results of these experiments demonstrated that muscular hypertrophy induced by $\beta$-agonists is probably a result of increased muscle protein synthesis capacity. Inhibition of sm-calpain mRNA expression suggests a role of sm-calpain in altered muscle protein metabolism by $\beta$-agonists.

Degree

Ph.D.

Advisors

Orcutt, Purdue University.

Subject Area

Livestock|Molecular biology|Food science

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