These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Cytochrome P-450-dependent biotransformation of a series of phenoxazone ethers in the rat conceptus during early organogenesis: evidence for multiple P-450 isoenzymes.
    Author: Yang HY, Namkung MJ, Juchau MR.
    Journal: Mol Pharmacol; 1988 Jul; 34(1):67-73. PubMed ID: 3393141.
    Abstract:
    Using highly sensitive probe-substrate analyses, investigations of drug biotransformation in tissues of the rat conceptus during an early stage of organogenesis revealed that three separate tissue components each contained P-450 isozymes capable of catalyzing the monooxygenation of foreign organic chemicals. Tissues of the embryo proper contained constitutive P450(s) that catalyzed readily measurable O-depentylation and O-debenzylation of pentoxyphenoxazone and benzyloxyphenoxazone, respectively, but no measurable O-demethylation of methoxyphenoxazone and barely detectable O-deethylation of ethoxyphenoxazone. Higher specific activities for the O-depentylation and O-debenzylation reactions were measured in preparations of the yolk sac and this organ also appeared to contain constitutive P450(s) for the readily detectable O-deethylation of ethoxyphenoxazone. The O-demethylation of methoxyphenoxazone could not be detected in the yolk sac. Only the O-debenzylation reaction could be detected in tissues of the ectoplacental cone. Treatment of conceptuses in utero with 3-methycholantherene (MC) resulted in significantly increased rates of O-deethylation reactions in preparations of yolk sac and embryo but not ectoplacental cone. Demethylation was not detectable in the same preparations. Treatment with phenobarbital, pregnenolone-16 alpha-carbonitrile, or isosafrole produced no observable effect on any of the reactions studied. Carbon monoxide (CO:O2 = 80:20 versus N2:O2 = 80:20) markedly inhibited all reaction rates and inhibition could be reversed by replacement of CO with N2. Deethylation and debenzylation were inhibited by anti-P450IA1 IgG after MC induction but were not affected by the same IgG fraction in untreated conceptuses. Depentylation reactions were not inhibited by anti-P450IA1 or anti-P450IIB1/2 antibodies under any of the conditions used. Deethylation was strongly inhibited by 1.0 microM 7,8-benzoflavone in tissues from MC-treated but not untreated conceptus. Metyrapone (0.1 mM) failed to significantly inhibit any of the measurable conceptus-catalyzed depentylation reaction. The results indicated the presence of four (or more) functional P450 isozymes in tissues of the conceptus during organogenesis, a constitutive depentylase(s) in the yolk sac and embryo, a constitutive deethylase(s) present in the yolk sac, an MC-inducible deethylase(s) in the embryo and yolk sac, and constitutive debenzylase(s) present in all three tissues. No O-demethylation was detectable in any of the three tissues, even after in utero exposure to inducers.(ABSTRACT TRUNCATED AT 400 WORDS)
    [Abstract] [Full Text] [Related] [New Search]