The effect of acute and chronic administration of the beta-agonist, cimaterol, on protein synthesis in ovine skin and muscle.
The action of intravenous infusion of the beta-agonist cimaterol (2.5 mg/d) on whole-body N retention and protein synthesis in peripheral tissues was examined in growing sheep. Wool growth was determined from skin patch clippings and adjusted to total fibre production. Protein synthesis was measured, using sequential large dose injections of [1-13C]valine, leucine and phenylalanine and then [ring-d5]phenylalanine, on biopsy samples from skin and m. longissimus dorsi taken before beta-agonist administration, at day 3 and day 15 of cimaterol infusion, and 15 d after withdrawal of the drug. Cimaterol increased total N retention by 1.9-2.3 g N/d (P < 0.01) over three successive 5 d periods. In contrast, wool growth was significantly reduced by 0.7 g N/d (P < 0.001) and the proportion of total N retained in wool declined from 0.71 to 0.25 (P < 0.01). The reduction in wool growth was accompanied by a decrease in protein fractional synthesis rate (FSR) in skin (11.6 v. 6.3%/d, P < 0.01). Muscle protein FSR, on the other hand, was markedly stimulated during cimaterol infusion (1.45 v. 3.01%/d, P < 0.001) as was RNA concentration (P < 0.001), RNA:protein (P < 0.001) and protein:DNA (P < 0.05). The estimated increase in total protein synthesis in muscle (+24 to 30 g/d) due to cimaterol administration was counterbalanced by reductions for skin (-25 to 27 g/d); this may account for the lack of changes in whole-body protein synthesis following beta-agonist administration reported in other studies. Although N retention rapidly returned to control values following withdrawal of the drug, both wool growth and skin protein synthesis remained depressed, while muscle protein FSR declined, but not to pre-treatment values. These results suggest a persistent action of cimaterol, but whether this is a function of residue concentrations or long-term metabolic responses is not known.