Anticatabolic effect of the beta 2-agonist cimaterol in vivo in tumor-bearing animals.
Loss of lean body mass occurs in cancer and may adversely affect outcome. The beta 2-agonist cimaterol increases muscle mass and protein content in tumor-bearing animals, in part by decreasing protein degradation, but the effect of the drug on protein synthesis remains uncertain. To determine the influence of cimaterol on protein synthesis, a methylcholanthrene sarcoma was transplanted sc into the dorsum of male Fischer-344 rats. After 3 weeks of tumor growth, tumor-bearing and control animals received daily sc injections of the beta 2-agonist cimaterol (0.15 mg/kg) for 5 days. Rate of protein synthesis was measured using iv [3H]-phenylalanine (25 microCi/100 g body wt) and cold phenylalanine (150 mumole/100 g body wt) in a flooding dose. Extensor digitorum longus muscles were harvested 10 min later, homogenized, and assayed for [3H]-phenylalanine uptake (bound) (dpm/mg muscle) and tissue-specific (free) radioactivity to determine protein synthesis rate (Ks: %/24 hr). There was a significant increase in protein synthesis rate in control and tumor-bearing animals receiving cimaterol compared to that in freely feeding, food-deprived, or matched-carcass-weight nontumor-bearing controls, as well as compared to that in tumor-bearing controls. We conclude that the anabolic effects of cimaterol are due to both decreased protein degradation and increased muscle protein synthesis. Therefore, beta 2-agonists may prove useful in prevention and/or treatment of cancer cachexia.
Stallion
A
A
Department of Surgery, University of Cincinnati Medical Center, Ohio, USA.
Foley-Nelson
T
T
Chance
W T
WT
James
J H
JH
Fischer
J E
JE
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight; D002100:Cachexia / Q000188:drug therapy / Q000209:etiology; D004435:Eating; D004983:Ethanolamines / Q000494:pharmacology*; D005508:Food Deprivation; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis / Q000187:drug effects; D018482:Muscle, Skeletal / Q000166:cytology; D009374:Neoplasms, Experimental / Q000150:complications / Q000188:drug therapy*; D010649:Phenylalanine / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D014316:Tritium
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D009124:Muscle Proteins; D014316:Tritium; D010649:Phenylalanine; C047411:cimaterol