Species difference and tissue distribution of uridine diphosphate-glucuronyltransferase activities toward E6080, 1-naphthol and 4-hydroxybiphenyl.
The apparent in vitro kinetic constants of uridine diphosphate-glucuronyltransferase (UDP-GT) activities towards E6080, 1-naphthol (1-N) and 4-hydroxybiphenyl (4-HB) were determined using microsomes, to assess the effect of inducing agents and evaluate species and tissue differences. In rats, the 3-methylcholanthrene and beta-naphthoflavone treatments increased the Vmax app/KM app values for E6080, 13- and 8-fold, and those for 1-N, 1.9- and 1.7-fold, respectively, but did not affect those for 4-HB. Phenobarbital was ineffective on the UDP-GT activity toward E6080. In rats and rhesus monkeys, the intestinal mucosa had higher specific UDP-GT activity toward E6080 than did the liver, and the rank order of the Vmax app/KM app value for E6080 in the intestinal mucosa was rhesus monkey > rat > guinea pig > beagle. In guinea pig, the Vmax app/KM app value for E6080 in the liver was 4 times higher than that in the intestinal mucosa. Both the Vmax app/KM app values for 1-N and 4-HB in the liver of all species studied were higher than those in the intestinal mucosa, and guinea pig liver showed the highest values, while, about the Vmax app for 1-N and 4-HB, beagle liver had the highest values. In the beagle intestinal mucosa, the Vmax app/KM app values for all 3 substrates studied were extremely low.(ABSTRACT TRUNCATED AT 250 WORDS)
Yoshimura
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Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.
Tanaka
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Horie
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D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000378:metabolism*; D004285:Dogs; D004790:Enzyme Induction; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006168:Guinea Pigs; D007413:Intestinal Mucosa / Q000201:enzymology; D007668:Kidney / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008253:Macaca mulatta; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008861:Microsomes / Q000201:enzymology; D008862:Microsomes, Liver / Q000201:enzymology; D009284:Naphthols / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013844:Thiazoles / Q000378:metabolism*; D014018:Tissue Distribution; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D001713:Biphenyl Compounds; D009284:Naphthols; D013844:Thiazoles; C064507:E 6080; C029350:1-naphthol; D008748:Methylcholanthrene; D019324:beta-Naphthoflavone; C019046:4-phenylphenol; D014453:Glucuronosyltransferase; D010634:Phenobarbital