Summary
The aim of the present study was to determine whether the anabolic effects of clenbuterol in rat skeletal muscle are mediated by ß2-adrenoceptor stimulation.
Female rats were treated with clenbuterol, alone or in combination with either the nonselective ß1/ß2-adrenoceptor antagonist sotalol, or the ß2-adrenoceptor-selective antagonist ICI118551. Clenbuterol caused an increase in muscle growth, accompanied by a reduction in ß2-adrenoceptor density in the rat hind-limb. Both actions were attenuated by sotalol. However, at the dose tested ICI118551 was the more effective antagonist of the muscle growth response, and when given alone, ICI118551 caused significant muscle atrophy. An increase in the weight of the heart was also observed in clenbuterol-treated rats, and again while this effect was attenuated by sotalol, it was reversed by ICI118551.
It is concluded that ß2-adrenoceptors mediate the anabolic effects of clenbuterol in cardiac and skeletal muscle, and that they play an important physiological role in the growth and maintenance of muscle mass in the rat hind-limb.
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References
Anon (1990) ß2 agonists in asthma: relief, prevention, morbidity. Lancet 336:1411–1412
Brockway JM, MacRae JC, Williams PEV (1987) Side effects of clenbuterol as a repartitioning agent. Vet Rec 20:381–383
Emery PW, Rothwell NJ, Stock MJ, Winter PD (1984) Chronic effects of ß2-adrenergic agonists on body composition and protein synthesis in the rat. Biosci Rep 4:83–91
Engelhardt G (1972) Struktur-Wirkungsbeziehungen in einer Reihe von neuen Amino-Halogen-substituierten Phenyl-aminoäthanolen. Arzneim-Forsch (Drug Res) 22:869–876
Greife HA, Klotz G, Berschauer F (1989) Effects of the phenethanolamine clenbuterol on protein and lipid metabolism in growing rats. J Anim Physiol Anim Nutr 61:19–27
Haves A, Cooper RG (1971) Studies on the absorption distribution and excretion of propranolol in rat, dog and monkey. J Pharmac Exp Ther 176:302–311
Jones LR, Besch HR, Fleming JW McConnaughey MM, Wantabe AM (1979) Separation of vesicles of cardiac sarcolemma from vesicles of cardiac sarcoplasmic reticulum. J Biol Chem 254:530–539
Kaumann AJ (1989) Is there a third heart, ß-adrenoceptor? Trends Pharmacol Sci 10:316–320
MacLennan PA, Edwards HT (1989) Effects of clenbuterol and propranolol on muscle mass: evidence that clenbuterol stimulates muscle ß-adrenoceptors to induce hypertrophy. Biochem J 264:573–579
Malta E (1976) The pharmacology of ß2-stimulants. PhD Thesis University of Melbourne, Melbourne VIC Australia
Maltin CA, Delday MI, Hay SM, Smith FG, Reeds PJ (1987) Propranolol apparently separates the physical and compositional characteristics of muscle growth induced by clenbuterol. Biosci Rep 7:51–56
McPherson GA, Malta E, Molenaar P, Raper C (1984) The affinity and efficacy of the selective ß1-adrenoceptor stimulant R0363 at ß1-and ß2-adrenoceptor sites. Br J Pharmac 82:897–904
Moretti-Rojas I, Ezrailson EG, Birnbaumer L, Entman ML, Garber AJ (1983) Serotonergic and adrenergic regulation of skeletal muscle metabolism in the rat. J Biol Chem 258:12499–12508
Munson PJ, Rodbard D (1980) Ligand: A versatile computerized approach for characterization of ligand-binding systems. Anal Biochem 107:220–239
Nolte D, Ulmer WT, Krieger E (1974) Lungenfunktionsuntersuchungen zur bronchospasmolytischen Wirkung der ß2-Adrenergika Salbutamol, Terbutalin und NAB 365 (Doppelblindversuch). ArzneimForsch (Drug Res) 24:858–860
O'Donnell SR (1976) Selectivity of clenbuterol (NAB365) in guinea-pig isolated tissues containing ß-adrenoceptors. Arch Int Pharmacodyn Ther 224:190–198
O'Donnell SR, Wanstall JC (1980) Evidence that ICI118551 is a potent, highly beta2-selective adrenoceptor antagonist and can be used to characterize beta-adrenoceptor populations in tissues. Life Sci 27:671–677
Reeds PJ, Hay SM, Dorwood PM, Palmer RM (1986) Stimulation of muscle growth by clenbuterol: lack of effect on muscle protein biosynthesis. Br J Nutr 56:249–258
Reeds PJ, Hay SM, Dorward PM, Palmer RM (1987) The effect of ß-agonists and antagonists on muscle growth and body composition of young rats. Comp Biochem Physiol 89:337–341
Rothwell NJ, Stock MJ, Sudera DK (1987) Changes in tissue blood flow and ß-receptor density of skeletal muscle in rats treated with the ß2-adrenoceptor agonist clenbuterol. Br J Pharmac 90:601–607
Sillence MN, Pegg GG, Lindsay DB (1991) Affinity of clenbuterol analogues for ß1-adrenoceptors in bovine skeletal muscle and the effect of these compounds on urinary nitrogen excretion in female rats. Naunyn-Schmiedeberg's Arch Pharmacol 344:442–448
Weiner N (1980) Drugs that inhibit adrenergic nerves and block adrenergic receptors. In: Goodman Gilman A, Goodman LS, Rall TW, Murad F (eds) The pharmacological basis of therapeutics. Macmillan, New York, pp 181–214
Yang YT, McElligott MA (1989) Multiple actions of ß-adrenergic agonists on skeletal muscle and adipose tissue. Biochem J 261:1–10
Zimmer A (1976a) Pharmacokinetics and metabolite patterns of clenbuterol in rabbit and dog. Arzneim-Forsch (Drug Res) 26:1442–1445
Zimmer A (1976b) Single and multiple applications and metabolic pattern of clenbuterol in man. Arzneim-Forsch (Drug Res) 26: 1446–1450
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Sillence, M.N., Matthews, M.L., Spiers, W.G. et al. Effects of clenbuterol, ICI118551 and sotalol on the growth of cardiac and skeletal muscle and on ß2-adrenoceptor density in female rats. Naunyn-Schmiedeberg's Arch Pharmacol 344, 449–453 (1991). https://doi.org/10.1007/BF00172585
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DOI: https://doi.org/10.1007/BF00172585