Document Detail


CYP2J subfamily cytochrome P450s in the gastrointestinal tract: expression, localization, and potential functional significance.
MedLine Citation:
PMID:  9187259     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular pharmacology     Volume:  51     ISSN:  0026-895X     ISO Abbreviation:  Mol. Pharmacol.     Publication Date:  1997 Jun 
Date Detail:
Created Date:  1997-07-14     Completed Date:  1997-07-14     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0035623     Medline TA:  Mol Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  931-43     Citation Subset:  IM    
Affiliation:
Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. zeldin@niehs.nih.gov
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MeSH Terms
Descriptor/Qualifier:
8,11,14-Eicosatrienoic Acid / 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:
P50-AG05128/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
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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