ANABOLIC EFFECTS OF CLENBUTEROL ON SKELETAL-MUSCLE ARE MEDIATED BY BETA(2)-ADRENOCEPTOR ACTIVATION

The potent anabolic effects of the beta-2-adrenoceptor agonist clenbuterol on skeletal muscle have been reported to be independent of actions on beta-adrenoceptors. In the present study clenbuterol, presented to rats in the diet (4 mg/kg), caused significant increases in gastrocnemius muscle mass, protein, and RNA content and a decrease in epididymal fat pad mass. These effects were not mimicked by oral administration of the beta-2-adrenoceptor agonist salbutamol even at high dose (52 mg/kg diet), and the effects of clenbuterol were not inhibited by addition of DL-propranolol (200 mg/kg diet). However, the selective beta-2-antagonist ICI-118,551 (200 mg/kg diet) reversed the anabolic effects of clenbuterol, and a high dose of DL-propranolol (1,000 mg/kg diet) also inhibited these actions of clenbuterol. Furthermore, continuous infusion of salbutamol (1.15 mg.kg body wt-1.day-1) via miniosmotic pumps did cause significant increases in muscle mass, protein, and RNA content. These results indicate that the anabolic effects of clenbuterol are dependent on interaction with the beta-2-adrenoceptor. However, a long duration of action appears to be required to induce the anabolic effects of beta-2-agonists.