Liver microsomal cytochrome P-450-dependent O-dealkylation reaction in various animals

Jpn J Pharmacol. 1983 Oct;33(5):1065-75. doi: 10.1254/jjp.33.1065.


Liver microsomal O-dealkylation activity was determined using O-methyl, O-ethyl and O-propyl derivatives of p-nitrophenol, 7-hydroxycoumarin (umbelliferon) and 7-hydroxyphenoxazone (resorufin) as substrates. Microsomal O-dealkylation activities of p-nitrophenol and 7-hydroxycoumarin O-alkyl derivatives were of similar levels, but the activities of 7-hydroxyphenoxazone O-alkyl derivatives were very low compared with those of other substrates. Pretreatment of rats with beta-naphthoflavone resulted in the preferential increase of O-deethylation and O-depropylation activities regardless of the ring structure of the substrates, and the ratio of O-deethylation and O-depropylation activities to that of O-demethylation increased markedly. On the other hand, the O-dealkylase activity of all substrates increased generally upon pretreatment of the rats with phenobarbital, but the ratio of O-deethylase or O-depropylase activity to that of O-demethylase in the pretreated rats was not very different from that of the untreated animals. Hexobarbital inhibited competitively the O-dealkylation activity in control and phenobarbital-pretreated rat microsomes. On the other hand, the O-dealkylase activity in microsomes obtained from beta-naphthoflavone-pretreated rats was inhibited remarkably by alpha-naphthoflavone, but not in microsomes prepared from untreated and phenobarbital-pretreated rats. Based on these results, this report discusses the relationship between the alteration of O-dealkylation activity and the composition change of cytochrome P-450 in microsomal membrane. Species differences in the substrate specificity of the O-dealkylation reaction and in the responsiveness of the animals to typical inducers were also observed using liver microsomes obtained from several animals under various conditions.

MeSH terms

  • Animals
  • Benzoflavones / pharmacology
  • Cytochrome P-450 Enzyme System / analysis*
  • Dealkylation
  • Guinea Pigs
  • Hexobarbital / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Microsomes, Liver / metabolism*
  • Phenobarbital / pharmacology
  • Rabbits
  • Rats
  • Rats, Inbred Strains
  • Species Specificity
  • beta-Naphthoflavone


  • Benzoflavones
  • beta-Naphthoflavone
  • Cytochrome P-450 Enzyme System
  • Hexobarbital
  • Phenobarbital