Effect of phenobarbital treatment and cytochrome P-450 inhibitors on the laurate ω- and (ω - 1)- hydroxylase activities of rat liver microsomes

R. T. Okita, S. S. Masters

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

The ω and (ω - 1)-hydroxylase activities for lauric acid were investigated in rat liver microsomes. Treatment of rats with phenobarbital selectively induced the hydroxylation of the fatty acid (ω - 1)-hydroxylase activity two- to threefold, but had only negligible effects on ω-hydroxylation. Metyrapone at 10-4 inhibited the specific activity of (ω - 1)-hydroxylase 70% in phenobarbital-pretreated rats, but produced only a 10% inhibition of the ω-hydroxylation activity. α-Naphthoflavone at 10-4 M inhibited (ω - 1)-hydroxylase activity 60% in untreated and β-naphthoflavone-pretreated rats, while ω-hydroxylase activity was decreased only 20%. A selective effect was also observed when microsomes were stored overnight at 4°C. Declines of 50% and 70% were observed in the (ω - 1)-hydroxylase activities after 24 and 48 hr, respectively, whereas ω-hydroxylation decreased only 10-20%. The differential effects on ω- and (ω - 1)-hydroxylase activities of a variety of conditions suggest that distinct cytochromes P-450 mediate the two fatty acid hydroxylases in liver microsomes.

Original languageEnglish (US)
Pages (from-to)147-151
Number of pages5
JournalDrug Metabolism and Disposition
Volume8
Issue number3
StatePublished - Jan 1 1980

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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