ω-Hydroxylation of 15-hydroxyeicosatetraenoic acid by lung microsomes from pregnant rabbits

R. T. Okita, R. J. Soberman, J. M. Bergholte, B. S. Masters, R. Hayes, R. C. Murphy

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

15-Hydroxyeicosatetraenoic acid (15-HETE) was converted by lung microsomes from pregnant rabbits to a polar metabolite that was identified by mass spectrometry as the 15,20-dihydroxyeicosatetraenoic acid. The formation of the 20- or ω-hydroxylated product was NADPH dependent, with a specific activity of 1.87 ± 0.53 nmol/min/mg of microsomal protein. Other hydroxylated derivatives of eicosatetraenoic acid that possessed hydroxy groups at the 5- and 12-carbon atoms were not metbolized by the lung microsomes. This hydroxylation of 15-HETE was observed in lung microsomes of pregnant rabbits and only minor amounts were formed by nonpregnant rabbits. The specific activity for 15-HETE ω-hydroxylation was similar to the value obtained for prostaglandin E1 (1.48 ± 0.33 nmol/min/mg). It is known that rabbit lungs possess a cytochrome P-450 that is induced during pregnancy and catalyzes the 20-hydroxylation of prostaglandins. The addition of the antibody to cytochrome P-450 prostaglandin ω-hydroxylase or prostaglandin E1, a substrate of this enzyme, resulted in potent inhibition of 15-HETE ω-hydroxylation, providing strong evidence that a common cytochrome P-450 catalyzes the ω-hydroxylation of both prostaglandin and 15-HETE.

Original languageEnglish (US)
Pages (from-to)706-709
Number of pages4
JournalMolecular pharmacology
Volume32
Issue number5
StatePublished - 1987

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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    Okita, R. T., Soberman, R. J., Bergholte, J. M., Masters, B. S., Hayes, R., & Murphy, R. C. (1987). ω-Hydroxylation of 15-hydroxyeicosatetraenoic acid by lung microsomes from pregnant rabbits. Molecular pharmacology, 32(5), 706-709.