| CYP2J subfamily cytochrome P450s in the gastrointestinal tract: expression, localization, and potential functional significance. | |
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MedLine Citation:
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PMID: 9187259 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Our laboratory recently described a new human cytochrome P450 arachidonic acid epoxygenase (CYP2J2) and the corresponding rat homologue (CYP2J3), both of which were expressed in extrahepatic tissues. Northern analysis of RNA prepared from the human and rat intestine demonstrated that CYP2J2 and CYP2J3 mRNAs were expressed primarily in the small intestine and colon. In contrast, immunoblotting studies using a polyclonal antibody raised against recombinant CYP2J2 showed that CYP2J proteins were expressed throughout the gastrointestinal tract. Immunohistochemical staining of formalin-fixed, paraffin-embedded intestinal sections using anti-CYP2J2 IgG and avidin-biotin-peroxidase detection revealed that CYP2J proteins were present at high levels in nerve cells of autonomic ganglia, epithelial cells, intestinal smooth muscle cells, and vascular endothelium. The distribution of this immunoreactivity was confirmed by in situ hybridization using a CYP2J2-specific antisense RNA probe. Microsomal fractions prepared from human jejunum catalyzed the NADPH-dependent metabolism of arachidonic acid to epoxyeicosatrienoic acids as the principal reaction products. Direct evidence for the in vivo epoxidation of arachidonic acid by intestinal cytochrome P450 was provided by documenting, for the first time, the presence of epoxyeicosatrienoic acids in human jejunum by gas chromatography/mass spectrometry. We conclude that human and rat intestine contain an arachidonic acid epoxygenase belonging to the CYP2J subfamily that is localized to autonomic ganglion cells, epithelial cells, smooth muscle cells, and vascular endothelium. In addition to the known effects on intestinal vascular tone, we speculate that CYP2J products may be involved in the release of intestinal neuropeptides, control of intestinal motility, and/or modulation of intestinal fluid/electrolyte transport. |
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Authors:
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D C Zeldin; J Foley; S M Goldsworthy; M E Cook; J E Boyle; J Ma; C R Moomaw; K B Tomer; C Steenbergen; S Wu |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Molecular pharmacology Volume: 51 ISSN: 0026-895X ISO Abbreviation: Mol. Pharmacol. Publication Date: 1997 Jun |
Date Detail:
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Created Date: 1997-07-14 Completed Date: 1997-07-14 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0035623 Medline TA: Mol Pharmacol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 931-43 Citation Subset: IM |
Affiliation:
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Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. zeldin@niehs.nih.gov |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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8,11,14-Eicosatrienoic Acid
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analogs & derivatives,
metabolism Animals Arachidonic Acid / metabolism Blotting, Northern Cytochrome P-450 Enzyme System / genetics, metabolism, physiology* Digestive System / enzymology*, metabolism Gas Chromatography-Mass Spectrometry Humans Immunoblotting Immunohistochemistry In Situ Hybridization Intestines / metabolism Isoenzymes / genetics, metabolism, physiology* Jejunum / metabolism Microsomes / metabolism Oxygenases / genetics, metabolism, physiology* RNA, Messenger / metabolism Rats |
| Grant Support | |
ID/Acronym/Agency:
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P50-AG05128/AG/NIA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Isoenzymes; 0/RNA, Messenger; 506-32-1/Arachidonic Acid; 7324-41-6/8,11,14-Eicosatrienoic Acid; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.13.-/Oxygenases; EC 1.14.14.1/arachidonate epoxygenase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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