Kobayashi Y, Yoshida T, Kotani E, Matsuura Y, Egawa H, Aoyagi T, Imaoka S, Funae Y, Tobinaga S, Kuroiwa Y
Showa College of Pharmaceutical Sciences, Tokyo, Japan.
Xenobiotica. 1995 Aug;25(8):779-89. doi: 10.3109/00498259509061893.
The effects of 4-phenylalkylpyridines (chain length of 0-5, 7, 9 and 11 carbon atoms) on the induction of hepatic microsomal P450 and its multiple forms (1A1/2 (1A1, 1A2), 3A2, 2B1/2, 2C6 and 2E1) in the male and female rat have been investigated. P450 induction gradually declined with increasing chain length of the 4-phenylalkylpyridines. Immunoblot analysis revealed that three pyridine compounds having methylene units of 0, 1 and 2 only induced P4501A2, whereas those having 4, 5 or 7 methylene units only induced 1A1 in the male rat. In the female rat, however, we could not observe such a chain length-dependent differential induction of the P4501A subfamily. Induced levels of P4503A2 and 2E1 were dependent on total P450 specific content, but 2C6 was increased in a chain length-dependent manner in both sexes. These results provide new information on the differential effects of pyridine-containing compounds on P450 induction in the rat.
研究了4-苯基烷基吡啶（碳原子链长度为0 - 5、7、9和11）对雄性和雌性大鼠肝微粒体P450及其多种形式（1A1/2（1A1、1A2）、3A2、2B1/2、2C6和2E1）诱导的影响。随着4-苯基烷基吡啶链长度的增加，P450诱导作用逐渐减弱。免疫印迹分析表明，仅具有0、1和2个亚甲基单元的三种吡啶化合物仅诱导P4501A2，而具有4、5或7个亚甲基单元的化合物仅在雄性大鼠中诱导1A1。然而，在雌性大鼠中，我们未观察到P4501A亚家族存在这种链长度依赖性差异诱导。P4503A2和2E1的诱导水平取决于总P450特异性含量，但2C6在两性中均以链长度依赖性方式增加。这些结果为含吡啶化合物对大鼠P450诱导的差异效应提供了新信息。
