The distribution of UDP-glucuronosyltransferases in rat liver parenchymal and nonparenchymal cells.
Activities for the glucuronidation of 1-naphthol, morphine and bilirubin as well as for the sulfation of 2-naphthol have been determined in homogenates of parenchymal, Kupffer and endothelial cells isolated from livers of untreated and Aroclor 1254-pretreated rats. In addition, Western blot analyses using different polyclonal antibodies against UDP-glucuronosyltransferases (UDP-GTs) were performed with similar preparations. All enzymes under investigation were expressed at high levels in liver parenchymal cells. The constitutive expression and inducibility of UDP-GT isozyme(s) for 1-naphthol glucuronidation was also clearly demonstrated in Kupffer and endothelial cells. Furthermore, the presence of other UDP-GT isozymes was detected in preparations from these cells. No significant sulfation of 2-naphthol was detectable in Kupffer and endothelial cell homogenates. While the glucuronidation of 1-naphthol and morphine was significantly induced in all cell types by Aroclor 1254-pretreatment of the animals, the glucuronidation of bilirubin and the sulfation of 2-naphthol remained unchanged. Since the specific activity of conjugation reactions is much lower in liver nonparenchymal cells than in liver parenchymal cells, and nonparenchymal cells contribute only about 6% to the total liver protein, protection of the cells themselves rather than contribution to the overall metabolism of xenobiotics seems to be the significant role of these xenobiotic-metabolizing enzymes in the sinusoidal lining cells.
Oesch
F
F
Institute of Toxicology, University of Mainz, Federal Republic of Germany.
Arand
M
M
Coughtrie
M W
MW
Burchell
B
B
Steinberg
P
P
D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D015239:Arylsulfotransferase / Q000378:metabolism*; D015153:Blotting, Western; D002469:Cell Separation; D020111:Chlorodiphenyl (54% Chlorine); D004727:Endothelium / Q000201:enzymology; D014453:Glucuronosyltransferase / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D007728:Kupffer Cells / Q000201:enzymology; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D001140:Aroclors; D007527:Isoenzymes; D020111:Chlorodiphenyl (54% Chlorine); D014453:Glucuronosyltransferase; D015239:Arylsulfotransferase