TY - JOUR
T1 - Modulation of UDP-glucuronosyltransferase 2B7 function by cytochrome P450s in vitro
T2 - Differential effects of CYP1A2, CYP2C9 and CYP3A4
AU - Takeda, Shuso
AU - Ishii, Yuji
AU - Mackenzie, Peter I.
AU - Nagata, Kiyoshi
AU - Yamazoe, Yasushi
AU - Oguri, Kazuta
AU - Yamada, Hideyuki
PY - 2005/10
Y1 - 2005/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=26444523430&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=26444523430&partnerID=8YFLogxK
U2 - 10.1248/bpb.28.2026
DO - 10.1248/bpb.28.2026
M3 - Article
C2 - 16204972
AN - SCOPUS:26444523430
SN - 0918-6158
VL - 28
SP - 2026
EP - 2027
JO - Biological and Pharmaceutical Bulletin
JF - Biological and Pharmaceutical Bulletin
IS - 10
ER -