UDP‐glucuronyltransferase in Perfused Rat Liver and in Microsomes: Influence of Phenobarbital and 3‐Methylcholanthrene

Abstract

Liver microsomal UDP‐glucuronyltransferase (1‐naphthol as substrate) is activated about 10‐fold by treatment of native microsomes in vitro with Triton X‐100. Following pretreatment of rats with 3‐methylcholanthrene or phenobarbital the specific activities of detergent‐activated microsomes were increased by about 300% and 40%, respectively, while the corresponding increases in native microsomes were only about 70% and 10%, respectively. In isolated liver perfused with 0.5 mM 1‐naphthol, the rate of glururonidation of naphthol, as determined by the appearance of naphthol glucuronide in the perfusate, bile and liver tissue, was 0.1 μmol × min −1 × g liver −1 . This rate of glucuronidation was increased by 70% in rats pretreated with 3‐methylcholanthrene and by 140% following phenobarbital treatment, in contrast to the changes observed in microsomes. A UDP‐glucuronic acid level of 0.3 μmol/g liver was determined in perfused liver from control rats. This level remained unchanged during perfusion with 0.5 mM 1‐naphthol. In the perfused liver from phenobarbital or 3‐methylcholanthrene‐treated rats, the UDP‐glucuronate level increased to 0.5 μmol/g liver. In control, 3‐methylcholanthrene or phenobarbital‐treated rats, rates of glucuronidation of 1‐naphthol in the perfused liver system correspond best with the UDP‐glucuronyltransferase activities determined in native microsomes when the different UDP‐glucuronate levels, microsomal protein contents and liver weights are taken into account. The results suggest that the enzyme is mostly latent in the microsomal membrane and that this latency is increased after pretreatment of rats with 3‐methylcholanthrene despite the marked enzyme induction.