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The effect of acute and chronic administration of the β-agonist, cimaterol, on protein synthesis in ovine skin and muscle

Published online by Cambridge University Press:  09 March 2007

J. E. Nash
Affiliation:
Department of Agriculture, University of Aberdeen, Aberdeen AB9 IUD
H. J. G. Rocha
Affiliation:
Rowett Research Institute, Bucksburn, Aberdeen AB2 9SB
V. Buchanz
Affiliation:
Rowett Research Institute, Bucksburn, Aberdeen AB2 9SB
G. A. Calder
Affiliation:
Rowett Research Institute, Bucksburn, Aberdeen AB2 9SB
E. Milne
Affiliation:
Rowett Research Institute, Bucksburn, Aberdeen AB2 9SB
J. F. Quirke
Affiliation:
Boehringer Ingelheim Vetmedica GMBH, 6507 Ingelheim, Germany
G. E. Lobley
Affiliation:
Rowett Research Institute, Bucksburn, Aberdeen AB2 9SB
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Abstract

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The action of intravenous infusion of the βagonist 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 [ l-I3C]valine, leucine and phenylalanine and then [ring-d,]-phenylalanine, on biopsy samples from skin and m. longissirnus dovsi taken before β-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 woo1 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 β-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

Type
Effects of hormones on protein synthesis
Copyright
Copyright © The Nutrition Society 1994

References

REFERENCES

Anderson, P. T., Helferich, W. G., Parkhill, L. C., Merkel, R. A. & Bergan, W. G. (1990). Ractopamine increases total and myofibrillar protein synthesis in cultured rat myotubes. Journal of Nutrition 120, 16771683.Google Scholar
Aoyagi, T., Adachi, K., Halprin, K. M. & Levine, V. (1980). The effects of epidermal growth factor on the cyclic nucleotide system in pig epidermis. Journal of Investigatory Dermatology 74, 238241.Google Scholar
Association of Official Analytical Chemists (1980). Official Methods of Analysis, 12th ed., Washington, DC: Association of Official Analytical Chemists.Google Scholar
Baker, P. K., Dalrymple, R. H., Ingle, D. L. & Ricks, C.A. (1984). Use of a P-adrenergic agonist to alter muscle and fat deposition in lambs. Journal of Animal Science 59, 12561261.Google Scholar
Bechet, D. M., Listrat, A, Delval, C., Ferrara, H. & Quirke, J. F. (1990). Cimaterol reduces cathepsin activities but has no anabolic effect in cultured myotubes. American Journal of Physiology 259, E822-E827.Google ScholarPubMed
Beermann, D. H., Butler, W. R., Hogue, D.E., Fishell, V.K., Dalrymple, R.H., Ricks, C.A. & Scanes, C.G. (1987). Cimaterol induced muscle hypertrophy and alternate endocrine status in lambs. Journal of Animal Science 65, 15141524.CrossRefGoogle Scholar
Beerman, D.H., Hogue, D.E., Fishell, V.K., Dalrymple, R.H. & Ricks, C.A. (1986). Effects of cimaterol and fish meal on performance, carcass characteristics and skeletal muscle growth in lambs. Journal of Animal Science 62, 37380.Google Scholar
Bergen, W.G., Johnson, S.M., Sjaerlund, D. M., Babiker, A.S., Ames, N.K., Merkel, R.A. & Anderson, D.A. (1989). Muscle protein metabolism in finishing pigs fed ractopamine. Journal of Animal Science 67, 22552262.Google Scholar
Bohorov, O., Buttery, P. J., Correia, J.H.R.D. & Soar, J.B. (1987). The effect of the β-2 adrenergic agonist clenbuterol or implantation with oestrogen plus trenbolone acetate in wether lambs. British Journal of Nutrition 57, 99107.Google Scholar
Calder, A.G., Anderson, S.E., Grant, I., McNurlan, M.A. & Garlick, P.J. (1992). The determination of low d,- phenylalanine enrichment (0.002–0.09 atom percent excess), after conversion to phenylethylamine, in relation to protein turnover studies by gas chromatography/electron ionization mass spectrometry. Rapid Communications in Mass Spectrometry 6, 421424.Google Scholar
Cameron, I.L. (1971). Cell proliferation and renewal in the mammalian body. In Cellular and Molecular Renewal in the Mammalian Body, pp. 4885 [Cameron, I.L. and Thrasher, J.D., editors]. New York: Academic Press.Google Scholar
Davis, H. L.Heinicke, E. A, Cook, R. A. & Kiernan, J. A. (1985). Partial purification from mammalian peripheral nerve of a trophic factor that ameliorates atrophy of denervated muscle. Experimental Neurology 89, 159171.Google Scholar
Davis, S. R., Barry, T. N. & Hughson, G. A. (1981). Protein synthesis in tissues of growing lambs. British Journal of Nutrition 46, 409419.CrossRefGoogle ScholarPubMed
Dawson, J. M., Buttery, P. J., Lammimamn, M. J., Soar, J. B., Essex, C. P., Gill, M. & Beever, D. E. (1991). Nutritional and endocrinological manipulation of lean deposition in forage-fed steers. British Journal of Nutrition 66, 171185.Google Scholar
Downes, A. M. & Sharry, L. F. (1971). Measurement of wool growth and its response to nutritional changes. Australian Journal of Biological Sciences 24, 117130.Google Scholar
Emery, P. W., Rothwell, N. J., Stock, J. J. & Winter, P. D. (1984). Chronic effects of β2, adrenergic agonists on body composition and protein synthesis in the rat. Bioscience Reports 4, 8391.Google Scholar
Garlick, P. J., Ferns, M. & Preedy, V. R. (1983). The effect of insulin infusion and food intake on muscle protein synthesis in postabsorptive rats. Biochemical Journal 210, 669676.Google Scholar
Gillespie, J. M. (1983). The structural proteins of hair: isolation, characterization, and regulation of biosynthesis. In Biochemistry and Physiology of the Skin, pp. 475510 [Goldsmith, L. A., editor]. New York: Oxford University Press.Google Scholar
Harris, P. M., Skene, P. A, Buchan, V., Milne, E., Calder, A. G., Anderson, S. E., Connell, A. & Lobley, G. E. (1992). Effect of food intake on hind-limb and whole body protein metabolism in growing lambs: chronic studies based on arterio-venous techniques. British Journal of Nutrition 68, 389407.Google Scholar
Helferich, W. G., Jump, D. B., Anderson, D. B., Skjaerlund, D. M., Merkel, R. A. & Bergan, W. G. (1990). Skeletal muscle a-actin synthesis is increased pretranslationally in pigs fed phenethanolamine ractopamine. Endocrinology 126, 30963100.Google Scholar
Hesketh, J. E., Campbell, G. P., Lobley, G. E., Maltin, C. A., Acamovic, F. & Palmer, R. M. (1992). Stimulation of actin and myosin synthesis in rat gastrocnemius muscle by clenbuterol; evidence for translation control. Comparative Biochemistry and Physiology 102, 2327.Google Scholar
Higgins, J. A., Lasslett, Y. V., Bardsley, R. G. & Buttery, P. J. (1988). The relation between dietary restriction or clenbuterol (a selective /3, agonist) treatment on muscle growth and calpain proteinase (EC 3.4.22.17. ) and calpastatin activities in lambs. British Journal of Nutrition 60, 645652.Google Scholar
Hovell, F. D. DeBKyle, D. J.Reeds, P. J. & Beermann, D. H. (1989). The effect of clenbuterol and cimaterol on the endogenous nitrogen loss in sheep. Nutrition Reports International 39, 11771182.Google Scholar
Hynd, P. I. (1982). Wool growth efficiency: a study of the effects of liveweight status and diet on wool growth. PhD Thesis, University of Adelaide, Australia.Google Scholar
Kretchmar, D. H., Hathaway, M. R., Epley, J. & Dayton, W. R. (1989). In vivo effect of a P adrenergic agonist on activity of calcium-dependent proteinases, their specific inhibitor, and cathepsins B and H in skeletal muscle. Archives of Biochemistry and Biophysics 215, 228235.CrossRefGoogle Scholar
Lobley, G. E. (1993). Species comparisons of tissue protein metabolism: effects of age and hormonal action. Journal of Nutrition 123, 337343.CrossRefGoogle ScholarPubMed
Lobley, G. E., Connell, A, Milne, E., Buchan, V., Calder, A. G., Anderson, S. E. & Vint, H. (1990). Muscle protein synthesis in response to testosterone administration in wether lambs. British Journal of Nutrition 64, 691704.Google Scholar
Lobley, G. E., Harris, P. M., Skene, P. A., Brown, D., Milne, E., Calder, A. G., Anderson, S. E., Garlick, P. J., Nevison, I. & Connell, A. (1992). Responses in tissue protein synthesis to sub- and supra-maintenance intake in growing sheep; comparison of large-dose, and continuous-infusion technique. British Journal of Nutrition 68,373388.Google Scholar
MacRae, J. C., Skene, P. A, Connell, A, Buchan, V. & Lobley, G. E. (1988). The action of the P-agonist clenbuterol on protein and energy metabolism in fattening wether lambs. British Journal of Nutrition 59, 457465.Google Scholar
Maltin, C. A, Hay, S. M., Delday, M. I., Lobley, G. E. & Reeds, P. J. (1989). The action of the P-agonist clenbuterol on protein metabolism in innervated and denervated phasic muscles. Biochemical Journal 261, 965971.Google Scholar
Maltin, C. A, Hay, S. M., Delday, M. I., Smith, F. G., Lobley, G. E. & Reeds, P. J. (1987). Clenbuterol, a beta agonist, induces growth in innervated and denervated rat soleus muscle via apparently different mechanisms. Bioscience Reports 1, 525532.CrossRefGoogle ScholarPubMed
Meyer, H. H. D. & Rinke, L. M. (1991). The pharmacokinetics and residues of clenbuterol in veal calves. Journal of Animal Science 69, 45384544.Google Scholar
Millward, D. J., Garlick, P. J., Nnanyelugo, D. O. & Waterlow, J. C. (1976). The relative importance of muscle protein synthesis and breakdown in the regulation of muscle mass. Biochemical Journal 156, 185.CrossRefGoogle ScholarPubMed
Nimrick, K., Hatfield, E. E., Kaminski, J. & Owens, F. N. (1970). Qualitative assessment of supplemental amino acid need for growing lambs fed urea as the sole nitrogen source. Journal of Nutrition 100, 12931300.Google Scholar
Rao, G. S., Del Monte, M. & Nadler, H. L. (1971). Adenyl cyclase activity in cultivated human skin fibroblasts. Nature New Biology 232, 253255.Google Scholar
Reeds, P. J., Hay, S. M., Donvard, P. M. & Palmer, R. M. (1986). Stimulation of muscle growth by clenbuterol: lack of effect on muscle protein biosynthesis. British Journal of Nutrition 56, 249258.Google Scholar
Reeds, P. J., Hay, S. M., Dorward, P. M. & Palmer, R. M. (1988). The effect of P-agonists and antagonists on muscle growth and body composition in young rats (Rattus sp.). Comparative Biochemistry and Physiology 89C, 337341.Google Scholar
Reis, P. J., Tunks, D. A. & Munro, S. G. (1990). Effects of the infusion of amino acids into the abomasum of sheep, with emphasis on the relative value of methionine, cysteine and homocysteine for wool growth. Journal of Agricultural Science (Comb) 114, 59.Google Scholar
Rocha, H. G., Nash, J., Connell, A. & Lobley, G. E. (1993). Protein synthesis in ovine muscle and skin: sequential measurements with three different amino acids based on the large dose procedure. Comparative Biochemistry and Physiology 105, 301307.Google Scholar
Sainz, R. D. & Wolff, J. E. (1987). Mechanisms of action of repartitioning agents: quantitative and dynamic evaluation of alternative hypotheses. Proceedings of the 2nd International Symposium on the Nutrition of Herbivores, pp. 153154. Brisbane: Australian Society of Animal Production.Google Scholar
Sainz, R. D. & Wolff, J. E. (1988). Effects of the /I-agonist, cimaterol, on growth, body composition and energy expenditure in rats. British Journal of Nutrition 60, 8590.Google Scholar
Sillence, M. N., Matthews, M. L., Spiers, W. G., Pegg, G. G. & Lindsay, D. B. (1991). Effects of clenbuterol, ICI 118551 and sotatol on the growth of cardiac and skeletal muscle and on β2,-adrenoceptor density in female rats. Naunyn-Schmiedeberg's Archivs fur Pharmacologia 344, 449453.Google Scholar
Slayden, O., Oldfield, J. E. & Stormshak, F. (1991). Growth and furring of mink (Mustela vison) given diets containing the β-adrenergic agonist, cimaterol. Animal Production 52, 377381.Google Scholar
Smith, S. B., Garcia, D. K. & Anderson, D. B. (1989). Elevation of specific mRNA in longissimus muscle of steers fed ractopamine. Journal of Animal Science 67, 34953502.Google Scholar
Storm, E. & Ørskov, E. R. (1984). The nutritive value of rumen microorganisms in ruminants. 4. The limiting amino acids of microbial protein in growing sheep determined by a new approach. British Journal of Nutrition 52, 613622.Google Scholar
Wang, S. Y. & Beermann, D. H. (1988). Reduced calcium dependent proteinase activity in cimaterol induced muscle hypertrophy in lambs. Journal of Animal Science 66, 25452550.Google Scholar
Weikard, R., Reichel, K. & Rehfeldt, C. (1992). Changes in protein synthesis, protein degradation and nucleic acid content in response to the beta-adrenergic agonist, clenbuterol, in muscles of rats. Archiv fur Tierzucht Dummerstorf 35, 421429.Google Scholar
Williams, P. E. V., Pagliani, L., Innes, G. M., Pennie, K., Harris, C. I. & Garthwaite, P. (1987). Effect of a &beta;agonist (clenbuterol) on growth, carcass composition, protein and energy metabolism of veal calves. British Journal of Nutrition 51, 417428.Google Scholar
Yang, Y. T. and McElligott, M. A. (1989). Multiple actions of /3-adrenergic agonists on skeletal muscle and adipose tissue. Biochemical Journal 261, 110.Google Scholar
Young, R. B., McGee, C. G., Moriarty, D. M., Richter, H. E., Campbell, M. R., Maupin, J. A. & Hudson, J. R. (1987). Protein metabolism in chicken muscle cell cultures treated with cimaterol. Federation Proceedings 46, 1020.Google Scholar