title: Modulation of UDP-glucuronosyltransferase 2B7 function by cytochrome P450s in vitro: differential effects of CYP1A2, CYP2C9 and CYP3A4.
abstract: Effects of cytochrome P450 isoforms, CYP1A2, CYP2C9 and CYP3A4, on the catalytic activity of UDP-glucuronosyltransferase 2B7 (UGT2B7) expressed in COS cell microsomal membranes were investigated using morphine as a substrate. When detergent-untreated COS cell microsomes were used as the enzyme source, the activity of morphine-3-glucuronide formation by UGT2B7 was reduced by addition of purified CYP1A2 and CYP2C9 in a concentration-dependent manner. The effect of CYP1A2 was greater than that of CYP2C9. In contrast, exogenous CYP3A4 had little effect on morphine glucuronidation activity. These results suggest that CYP1A2 and CYP2C9 have ability to modify UGT2B7 function. However, the mechanism(s) underlying the modulation of UGT2B7 function by these P450s seems to differ from that by CYP3A4.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University; Fukuoka 812-8582, Japan.
authors.forename: Shuso
authors.initials: S
authors.lastname: Takeda
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ishii
authors.forename: Peter I
authors.initials: PI
authors.lastname: Mackenzie
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Nagata
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yamazoe
authors.forename: Kazuta
authors.initials: K
authors.lastname: Oguri
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamada
mesh_terms: D000818:Animals; D019556:COS Cells; D002384:Catalysis; D002522:Chlorocebus aethiops; D003577:Cytochrome P-450 Enzyme System / Q000145:classification / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000378:metabolism*; D008861:Microsomes / Q000201:enzymology; D013379:Substrate Specificity
chemical_list: D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase