Species difference and tissue distribution of uridine diphosphate-glucuronyltransferase activities toward E6080,...

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)