Effect of theophylline on urinary excretion of 3-methylhistidine in patients with lung disease.
Theophylline, which is commonly used for the treatment of lung disease, has been reported to stimulate lipolysis, glycogenolysis, and gluconeogenesis. This study was initiated to investigate whether theophylline therapy also induces catabolic changes in protein metabolism and thus provides additional substrates for energy metabolism. Urinary excretion of 3-methylhistidine (3-MH) as an index of myofibrillar protein catabolism was measured at the end of a 7-day treatment period with theophylline and a 5-day basal untreated control period in eight patients with stable chronic obstructive pulmonary disease (COPD), eight patients with stable asthma, and eight normal healthy volunteers. Basal urinary 3-MH excretion and 3-MH/creatinine ratios, and nutritional indices assessed were not different in the three groups. Under similar drug (except theophylline), dietary, and activity regimens, comparison of the two experimental periods showed that theophylline increased mean urinary 3-MH excretion and 3-MH/creatinine ratios in all three groups of subjects. These changes were significant in the COPD and asthmatic patients (mean 3-MH +/- SD, mumol/d: basal, 176 +/- 46 v 206 +/- 46; and basal, 190 +/- 27 v 216 +/- 45, respectively, P less than .05) and persisted when 3-MH values were normalized to creatinine excretion (15% to 38%, P less than .005). In contrast, the mean increment was marginal in the group of normal volunteers and this discrepancy of effect between groups may be attributed to dietary noncompliance. Furthermore, the response of the COPD group was significantly greater than the asthmatic and control groups (1.8x and 11.3x, respectively, P less than .05). In conclusion, these results suggest that theophylline may enhance myofibrillar protein degradation.(ABSTRACT TRUNCATED AT 250 WORDS)
Wei
I W
IW
Airway Disease Center, Case Western Reserve University, Cleveland, OH.
McFadden
E R
ER
Hoppel
C L
CL
D000328:Adult; D000368:Aged; D001249:Asthma / Q000652:urine*; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000652:urine; D005260:Female; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000652:urine*; D008297:Male; D008762:Methylhistidines / Q000652:urine*; D008875:Middle Aged; D009752:Nutritional Status; D009994:Osmolar Concentration; D010865:Pilot Projects; D013806:Theophylline / Q000494:pharmacology*
D008762:Methylhistidines; D003404:Creatinine; D013806:Theophylline; C028118:3-methylhistidine