Metabolism of prostaglandins and xenobiotics by adrenal microsomal monooxygenase in the guinea pig

David Kupfer, Javier Navarro, Gregory K. Miranda, Anthony D. Theoharides

Research output: Contribution to journalArticle

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Abstract

The possibility that prostaglandins could serve as substrates for the guinea pig adrenal microsomal monooxygenase was investigated. The binding of PGE1 to adrenal microsomes was found to exhibit a reverse type I spectral change. Also PGE1 diminished the magnitude of type I spectrum elicited by cortisol binding to adrenal microsomes. The incubation of [3H]PGE1 or of [3H]PGE2 with adrenal microsomes supplemented with NADPH yielded primarily the respective 19-hydroxy metabolite. The enzymatic activity catalyzing this hydroxylation appears to be a typical monooxygenase, requiring NADPH for activity and being strongly inhibited by metyrapone, SKF 525A, and cytochrome c. Carbon monoxide at a ratio of 9:1 to oxygen moderately inhibited the hydroxylation of PGE1. Whereas the liver catalyzed the hydroxylation of PGE1 and PGA1 equally well, the adrenal microsomes preferentially catalyzed the hydroxylation of PGE1. This finding and the observation that α-naphthoflavone is a weak inhibitor of the adrenal PGE1 hydroxylation points to significant differences between the adrenal and liver prostaglandin hydroxylation activities. Cortisol, which is a substrate for adrenal monooxygenase, strongly inhibited PGE1 and PGE2 hydroxylation. By contrast, certain xenobiotics (ethylmorphine, hexobarbital, benzpyrene), which are also metabolized by adrenal microsomes, only slightly inhibited the hydroxylation of PGE1. Similarly, PGE1 only weakly inhibited ethylmorphine and benzphetamine demethylation and hexobarbital hydroxylation. These observations suggest that adrenal microsomes contain several monooxygenases with different affinities for prostaglandins and for the different xenobiotic substrates.

Original languageEnglish (US)
Pages (from-to)297-307
Number of pages11
JournalArchives of Biochemistry and Biophysics
Volume205
Issue number2
DOIs
StatePublished - 1980
Externally publishedYes

Fingerprint

Aryl Hydrocarbon Hydroxylases
Alprostadil
Hydroxylation
Xenobiotics
Metabolism
Prostaglandins
Guinea Pigs
Microsomes
Ethylmorphine
Mixed Function Oxygenases
Hexobarbital
NADP
Dinoprostone
Liver
Hydrocortisone
Substrates
Benzopyrenes
Benzphetamine
Proadifen
Metyrapone

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Metabolism of prostaglandins and xenobiotics by adrenal microsomal monooxygenase in the guinea pig. / Kupfer, David; Navarro, Javier; Miranda, Gregory K.; Theoharides, Anthony D.

In: Archives of Biochemistry and Biophysics, Vol. 205, No. 2, 1980, p. 297-307.

Research output: Contribution to journalArticle

Kupfer, David ; Navarro, Javier ; Miranda, Gregory K. ; Theoharides, Anthony D. / Metabolism of prostaglandins and xenobiotics by adrenal microsomal monooxygenase in the guinea pig. In: Archives of Biochemistry and Biophysics. 1980 ; Vol. 205, No. 2. pp. 297-307.
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