title: Optimal detergent activation of rat liver microsomal UDP-glucuronosyl transferases toward morphine and 1-naphthol: contribution to induction and latency studies.
abstract: The detergent-activation profiles of UDP-glucuronosyl transferases (UGTs, EC 2.4.1.17) toward 1-naphthol and toward morphine have been determined: three non-ionic detergents, Triton X-100, Brij 58 and Lubrol Px and one zwitterion detergent, 3-(3-cholamidopropyl)-dimethylammonio-1-propanesulfonic acid (CHAPS) were studied. The results showed that marked inhibition of 1-naphthol-UGT and morphine UGT activities occurred with high concentrations of Triton X-100. Lubrol Px, at high concentrations, inhibited 1-naphthol-UGT but not morphine-UGT. It appeared that the detergent/protein ratio suitable for optimal activation of both isoenzymes was limited to 0.2 for these detergents. In contrast, Brij 58 and CHAPS displayed optimal activation of the two enzymes for a large range of detergent/microsomal protein ratios (respectively from 0.2 to 1 and from 0.4 to 1), making them the most suitable for induction and/or latency studies of both isoenzymes. The influence of maximal activation status on the effect of 3-methylcholanthrene and phenobarbital treatment on morphine-UGT and 1-naphthol-UGT activity has also been evaluated. The findings provided evidence that detergent-activation profiles and optimal detergent-activated versus "native" UGT activity determination give crucial informations about the characteristics of a given isoenzymic form of UGT, i.e. its sensitivity to specific alterations of the phospholipid environment, its latency and its inducibility.
authors.affiliation: Départment de Recherche sur la Sécurité du médicament, Rhône-Poulenc Rorer, Vitry sur Seine, France.
authors.forename: E
authors.initials: E
authors.lastname: Lett
authors.forename: W
authors.initials: W
authors.lastname: Kriszt
authors.forename: V
authors.initials: V
authors.lastname: de Sandro
authors.forename: G
authors.initials: G
authors.lastname: Ducrotoy
authors.forename: L
authors.initials: L
authors.lastname: Richert
mesh_terms: D000818:Animals; D003902:Detergents / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008748:Methylcholanthrene; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D009020:Morphine / Q000378:metabolism*; D009284:Naphthols / Q000378:metabolism*; D010634:Phenobarbital; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D003902:Detergents; D007527:Isoenzymes; D009284:Naphthols; C029350:1-naphthol; D008748:Methylcholanthrene; D009020:Morphine; D014453:Glucuronosyltransferase; D010634:Phenobarbital