TY - JOUR
T1 - Caffeine metabolism in liver slices during postnatal development in the rat
AU - Warszawski, Ditza
AU - Ben-Zvi, Zvi
AU - Gorodischer, Rafael
PY - 1981/12/1
Y1 - 1981/12/1
N2 - The metabolism of caffeine was investigated in liver slices of young and adult rats. Liver slices from adult male rats metabolized caffeine at an initial rate of 48.31 ± 3.71 nmoles · (g liver)-1 · hr-1 to four main metabolite fractions. By a combination of thin-layer radiochromatography and high performance liquid chromatography, theophylline, paraxanthine and 1, 3, 7-trimethyldihydrouric acid were identified as caffeine metabolites. Apparent Vmax of the overall reaction was 83.30 nmoles caffeine metabolites formed · (g liver)-1 · hr-1. Theophylline competitively inhibited caffeine metabolism [the apparent Km was 19.20, μM in the absence of theophylline, the apparent ki was 36.50 μM in the presence of theophylline (100 μM)]. SKF 525-A inhibited caffeine metabolism; the formation of all of the metabolite fractions was inhibited to a similar extent. Allopurinol (100 μM) had no effect. The specific activity of the enzyme system was extremely low when liver slices of 2-day-old-rats were used [1.46 ± 0.08 nmoles caffeine metabolites formed · (g liver)-1 · hr-1]; the reaction velocity increased gradually with increasing age and reached a peak [52.26 ± 1.41 nmoles caffeine metabolites formed · (g liver)-1 · hr-1]at 30 days of age. Changes in the formation of the four metabolite fractions with age followed the pattern of the overall caffeine metabolism. These results demonstrate that the liver of the newborn rat has an extremely limited capacity to metabolize caffeine in vitro and are consistent with the proposed involvement of the liver microsomal cytochromes P-450 monooxygenase system in the metabolism of caffeine. N-Demethylation is the main pathway of in vitro caffeine metabolism in the rat liver at all ages.
AB - The metabolism of caffeine was investigated in liver slices of young and adult rats. Liver slices from adult male rats metabolized caffeine at an initial rate of 48.31 ± 3.71 nmoles · (g liver)-1 · hr-1 to four main metabolite fractions. By a combination of thin-layer radiochromatography and high performance liquid chromatography, theophylline, paraxanthine and 1, 3, 7-trimethyldihydrouric acid were identified as caffeine metabolites. Apparent Vmax of the overall reaction was 83.30 nmoles caffeine metabolites formed · (g liver)-1 · hr-1. Theophylline competitively inhibited caffeine metabolism [the apparent Km was 19.20, μM in the absence of theophylline, the apparent ki was 36.50 μM in the presence of theophylline (100 μM)]. SKF 525-A inhibited caffeine metabolism; the formation of all of the metabolite fractions was inhibited to a similar extent. Allopurinol (100 μM) had no effect. The specific activity of the enzyme system was extremely low when liver slices of 2-day-old-rats were used [1.46 ± 0.08 nmoles caffeine metabolites formed · (g liver)-1 · hr-1]; the reaction velocity increased gradually with increasing age and reached a peak [52.26 ± 1.41 nmoles caffeine metabolites formed · (g liver)-1 · hr-1]at 30 days of age. Changes in the formation of the four metabolite fractions with age followed the pattern of the overall caffeine metabolism. These results demonstrate that the liver of the newborn rat has an extremely limited capacity to metabolize caffeine in vitro and are consistent with the proposed involvement of the liver microsomal cytochromes P-450 monooxygenase system in the metabolism of caffeine. N-Demethylation is the main pathway of in vitro caffeine metabolism in the rat liver at all ages.
UR - http://www.scopus.com/inward/record.url?scp=0019789998&partnerID=8YFLogxK
U2 - 10.1016/0006-2952(81)90511-6
DO - 10.1016/0006-2952(81)90511-6
M3 - Article
C2 - 7317099
AN - SCOPUS:0019789998
SN - 0006-2952
VL - 30
SP - 3145
EP - 3150
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 23
ER -