Modulation of UDP-glucuronosyltransferase 2B7 function by cytochrome P450s in vitro:: Differential effects of CYP1A2, CYP2C9 and CYP3A4
Modulation of UDP-glucuronosyltransferase 2B7 function by cytochrome P450s in vitro:: Differential effects of CYP1A2, CYP2C9 and CYP3A4
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DOI：
10.1248/bpb.28.2026
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发表时间：
2005-10-01
影响因子：
2
通讯作者：
Yamada, H
中科院分区：
文献类型：
--
作者：
Takeda, S;Ishii, Y;Yamada, H
以吗啡为底物，研究了细胞色素P450的3种亚型（CYP 1A 2、CYP 2C 9和CYP 3A 4）对COS细胞微粒体膜表达的UDP-葡萄糖醛酸基转移酶2B 7（UGT 2B 7）催化活性的影响。当使用未处理去污剂的COS细胞微粒体作为酶源时，通过添加纯化的CYP 1A 2和CYP 2C 9以浓度依赖性方式降低UGT 2B 7形成吗啡-3-葡糖苷酸的活性。CYP 1A 2的作用大于CYP 2C 9。相反，外源性CYP 3A 4对吗啡葡萄糖醛酸化活性几乎没有影响。这些结果表明，CYP 1A 2和CYP 2C 9具有修饰UGT 2B 7功能的能力。然而，这些P450调节UGT 2B 7功能的潜在机制似乎与CYP 3A 4不同。
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.