Functional heterogeneity of UDP-glucuronosyltransferase activities in C57BL/6 and DBA/2 mice

Functional heterogeneity of liver microsomal UDP-glucuronosyltransferase activities towards 1-naphthol, 4-methylumbelliferone or 3-hydroxybenzo(a)pyrene (UDP-GT1 activities) and morphine or 4-hydroxybiphenyl (UDP-GT2 activities) was studied in two inbred strains of mice which are genetically responsive (C57BL/6) or non-responsive (DBA/2) to 3-methylcholanthrene-induction of drug metabolizing enzymes. 3-Methylcholanthrene preferentially induced UDP-GT1 activities in C57BL/6 mice. Phenobarbital, however, at low doses (50 mg/kg), selectively induced UDP-GT2 activities. Higher doses of phenobarbital (80 mg/kg) induced both UDP-GT1 and UDP-GT2 activities. In DBA/2 mice 3-methylcholanthrene-induction of UDP-glucuronosyltransferase activities was not detectable whereas enzyme induction by phenobarbital appeared to be unimpaired. UDP-GT1 activities were ubiquitously detectable in mouse tissues whereas appreciable UDP-GT2 activities were only found in liver and small intestinal mucosa. UDP-GT1 (1-naphthol as substrate) was not inhibited by morphine suggesting different active sites for the conjugation of these substrates. The results suggest the presence of at least two functionally different forms of UDP-glucuronosyltransferase in mice. In conjunction with the results of Owens (J. biol. Chem. 252, 2827 (1977)) it is evident that one of these enzyme forms is regulated by the Ah locus.