Species Difference and Tissue Distribution of Uridine Diphosphate-Glucuronyltransferase Activities toward E6080, 1-Naphthol and 4-Hydroxybiphenyl

抄録

The apparent in vitro kinetic constants of uridine diphosphate-glucuronyltranferase (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 β-naphthoflavone treatments increased the V_{max app}/K_{M 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 V_{max app}/K_{M app} value for E6080 in the intestinal mucosa was rhesus monkey>rat>guinea pig>beagle. In guinea pig, the V_{max app}/K_{M app} value for E6080 in the liver was 4 times higher than that in the intestinal mucosa. Both the V_{max app}/K_{M 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 V_{max app} for 1-N and 4-HB, beagle liver had the highest values. In the beagle intestinal mucosa, the V_{max app}/K_{M app} values for all 3 substrates studied were extremely low. Though E6080 and 1-N are both cleassed as GT-1 substrate, the ratio of UDP-GT activity toward E6080 to that toward 1-N was higher in the intestinal mucosa than that in the liver, which indicates a tissue difference in the population of UDP-GT isozymes