Immunochemical and functional characterization of UDP-glucuronosyltransferases from rat liver, intestine and kidney.
Glucuronidation of various substrates in hepatic, intestinal and renal microsomes of control, phenobarbital (PB), 3-methylcholanthrene (3MC) and Aroclor-1254 (A1254) pretreated rats was investigated. UDPGT activities tested could be divided in four groups on the basis of their tissue distribution and induction by PB or 3MC in liver microsomes. GT1 activities (1-naphthol, benzo(a)pyrene-3,6-quinol) are induced by 3MC in liver microsomes and are present in all tissues investigated. GT2 activities (morphine, 4-hydroxybipheynl) are induced by PB in liver microsomes and appear to be restricted to the liver and the intestine. UDPGT activity towards bilirubin, although induced by PB, can be detected in hepatic, intestinal and renal microsomes. UDPGT activity towards fenoterol is restricted to the liver and intestine and is not induced by PB, 3MC or A1254. The presence of inducible immunoreactive UDPGT isoenzymes in microsomes of liver, intestine and kidney of control and induced rats was demonstrated by immunoblot analysis using rabbit anti-rat liver-GT1 antibodies. Induction of both 54 and 56 kDa polypeptides in hepatitis, intestinal and renal microsomes by 3MC or A1254 was observed. Purification of UDPGT (1-naphthol as substrate) from intestinal microsomes to apparent homogeneity yielded a polypeptide with an apparent molecular weight of 54-56 kDa. The results indicate that 54 and 56 kDa UDPGT polypeptides are the major A1254 inducible isoenzymes in intestinal and renal microsomes. An increase in immunoreactive protein is correlated with a biochemically measurable increase in glucuronidation capacity for GT1 substrates.
D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D020111:Chlorodiphenyl (54% Chlorine); D004790:Enzyme Induction; D014453:Glucuronosyltransferase / Q000096:biosynthesis* / Q000276:immunology; D007422:Intestines / Q000201:enzymology*; D007527:Isoenzymes / Q000096:biosynthesis; D007668:Kidney / Q000201:enzymology*; D008099:Liver / Q000201:enzymology*; D008748:Methylcholanthrene / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D001140:Aroclors; D007527:Isoenzymes; D020111:Chlorodiphenyl (54% Chlorine); D008748:Methylcholanthrene; D014453:Glucuronosyltransferase