Effect of thyroid hormone on the substrate interaction with P-450 in the oxidation of drugs by liver microsomes.
Effect of thyroid hormone on the substrate interaction with P-450 in the oxidation of drugs by liver microsomes.
复制标题
甲状腺激素对肝微粒体药物氧化过程中底物与 P-450 相互作用的影响。
DOI：
10.1093/oxfordjournals.jbchem.a129395
复制
发表时间：
1970
影响因子：
2.7
通讯作者：
A. Takahashi
中科院分区：
文献类型：
--
作者：
R. Kato;A. Takanaka;A. Takahashi
雄性大鼠给予甲状腺素可降低肝微粒体中P-450的含量和各种药物引起的P-450光谱变化幅度。六巴比妥和氨基比林诱导的P-450光谱变化幅度减小，而苯胺和唑唑胺诱导的P-450光谱变化幅度无显著影响。与雄性大鼠相比，六巴比妥和氨基比林在甲状腺素处理的雌性大鼠微粒体中引起的光谱变化幅度没有明显降低。这些结果表明，甲状腺素降低了P-450与己巴比妥和氨基比林的结合能力，可能是通过破坏雄激素作用来增加P-450的结合能力。P-450与六巴比妥和氨基比林结合能力的下降被认为是六巴比妥羟基化和氨基比林n -去甲基化活性下降的一个负责任的因素。
The administration of thyroxine to male rats decreased the content of P-450 and the magnitude of spectral change of P-450 induced by various drugs in hepatic microsomes. The magnitudes of spectral changes per P-450 induced by hexobarbital and aminopyrine were decreased, whereas those induced by aniline and zoxazolamine were not significantly affected.In contrast to the results observed with male rats, the magnitudes of the spectral changes induced by hexobarbital and aminopyrine were not significantly decreased in microsomes from thyroxine-treated female rats. These results suggest that the binding capacity of P-450 with hexobarbital and aminopyrine was decreased by thyroxine probably through an impairment of androgen action to increase the binding capacity of P-450. The decrease in the binding capac ity of P-450 with hexobarbital and aminopyrine is assumed to be a responsible factor for the decrease in the activities of hexobarbital hydroxylation and aminopyrine N-demethylation.