Emi Y, Omura T
Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Fukuoka.
J Biochem. 1988 Jul;104(1):40-3. doi: 10.1093/oxfordjournals.jbchem.a122418.
The effects of phenobarbital (PB), 3-methylcholanthrene (MC), and alpha-naphthoflavone (alpha-NF) on the synthesis of drug-inducible forms of cytochrome P-450, P-450(PB-1), and P-450(MC-1), and sex-specific forms of cytochrome P-450, P-450(M-1), and P-450(F-1), in male and female rats were studied. Whereas P-450(PB-1) and P-450(MC-1) in liver microsomes were markedly induced in both sexes by treatment with PB and MC, respectively, the contents of P-450(M-1) and P-450(F-1) were significantly decreased by the treatments. alpha-NF, which is not a P-450 inducer, did not change the contents of sex-specific forms of cytochrome P-450. The translatable mRNAs of the P-450s were also determined by using an in vitro translation system. The mRNAs coding for P-450(PB-1) and P-450(MC-1) were increased by drug administrations. On the other hand, the mRNAs coding for P-450(M-1) and P-450(F-1) were transiently decreased by the drugs, and then returned to the normal levels. The time courses of the induction of the drug-inducible P-450s and the repression of the sex-specific P-450s showed no close correlation. alpha-NF had no effect on the synthesis of P-450(M-1) and P-450(F-1). We also found that the synthesis of P-450(M-1) in the livers of untreated rats showed no diurnal variations.
研究了苯巴比妥（PB）、3-甲基胆蒽（MC）和α-萘黄酮（α-NF）对雄性和雌性大鼠中药物诱导型细胞色素P-450、P-450（PB-1）和P-450（MC-1）以及细胞色素P-450的性别特异性形式P-450（M-1）和P-450（F-1）合成的影响。虽然用PB和MC分别处理后，肝微粒体中的P-450（PB-1）和P-450（MC-1）在两性中均被显著诱导，但处理后P-450（M-1）和P-450（F-1）的含量显著降低。α-NF不是P-450诱导剂，它没有改变细胞色素P-450性别特异性形式的含量。还使用体外翻译系统测定了P-450的可翻译mRNA。编码P-450（PB-1）和P-450（MC-1）的mRNA因药物给药而增加。另一方面，编码P-450（M-1）和P-450（F-1）的mRNA因药物而短暂降低，然后恢复到正常水平。药物诱导型P-450的诱导和性别特异性P-450的抑制的时间进程没有密切相关性。α-NF对P-450（M-1）和P-450（F-1）的合成没有影响。我们还发现，未处理大鼠肝脏中P-450（M-1）的合成没有昼夜变化。
