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Mechanisms by which ractopamine and other beta-adrenergic agonists stimulate skeletal muscle growth are discussed. Oral administration dose-response studies in surgically altered laboratory animals provide evidence that indirect endocrine-mediated effects are not an essential component of efficacy. Results from age-comparison studies in laboratory animals and livestock species provide evidence that metabolic maturity of skeletal muscle may be a critical factor with regard to efficacy, suggesting that receptor presence and density are important. Temporal studies demonstrate the rapidity of responses associated with protein and lipid metabolism changes, and that progressive decline in rate of anabolic response in skeletal muscle results from chronic administration. Associated results that demonstrate progressive beta-adrenergic receptor density reductions are observed and suggest, likewise, that protein accretion rate and muscle growth rate responses are receptor-mediated. Measurement of in vivo metabolic effects resulting from continuous systemic infusion has been conducted in relatively few experiments. Detailed blood flow and hind limb net flux data are available for a single beta-agonist, cimaterol. Kinetics studies and close arterial infusion of cimaterol in the hind limb of growing cattle demonstrate large transient increases in amino acid extraction from the circulation and similar patterns of net uptake when compared with the contralateral control saline-infused hind limb. Predictions of differential net effects on protein accretion using integration of essential amino acid net flux measurements are corroborated by quantitative documentation of protein mass differences in individual muscles from treated and control hind limbs. Definitive descriptions of specific pathway mechanism(s) of action for increasing protein synthesis have not as yet been reported. Therefore, additional research is required for elucidation of cellular and intracellular components of mechanism(s) of action.
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D. H. Beermann (2002) studied this question.
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