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Laboratories of
Pulmonary Pathobiology (D.C.Z., M.E.C., J.E.B.,
J.M., C.R.M., S.W.),
Experimental Pathology (J.F.), and
Molecular
Biophysics (K.B.T.), National Institute of Environmental Health
Sciences, Research Triangle Park, North Carolina 27709, Pathology
Associates International (S.M.G.), Durham, North Carolina 27713, and
Department of Pathology (C.S.), Duke University Medical Center, Durham,
North Carolina 27710
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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 H. Sakai, Y. Ohira, A. Tanaka, T. Suzuki, A. Ikari, M. Morii, and N. Takeguchi Inhibition of small-conductance Cl- channels by the interleukin-1{beta}-stimulated production of superoxide in rabbit gastric parietal cells J. Physiol., August 15, 2003; 551(1): 207 - 217. [Abstract] [Full Text] [PDF]
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S. Matsumoto, T. Hirama, T. Matsubara, K. Nagata, and Y. Yamazoe Involvement of CYP2J2 on the Intestinal First-Pass Metabolism of Antihistamine Drug, Astemizole Drug Metab. Dispos., November 1, 2002; 30(11): 1240 - 1245. [Abstract] [Full Text] [PDF]
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L. M. King, J. Ma, S. Srettabunjong, J. Graves, J. A. Bradbury, L. Li, M. Spiecker, J. K. Liao, H. Mohrenweiser, and D. C. Zeldin Cloning of CYP2J2 Gene and Identification of Functional Polymorphisms Mol. Pharmacol., April 1, 2002; 61(4): 840 - 852. [Abstract] [Full Text] [PDF]
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 J. M. Lasker, W. B. Chen, I. Wolf, B. P. Bloswick, P. D. Wilson, and P. K. Powell Formation of 20-Hydroxyeicosatetraenoic Acid, a Vasoactive and Natriuretic Eicosanoid, in Human Kidney. ROLE OF CYP4F2 AND CYP4A11 J. Biol. Chem., February 11, 2000; 275(6): 4118 - 4126. [Abstract] [Full Text] [PDF]
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J. Ma, W. Qu, P. E. Scarborough, K. B. Tomer, C. R. Moomaw, R. Maronpot, L. S. Davis, M. D. Breyer, and D. C. Zeldin Molecular Cloning, Enzymatic Characterization, Developmental Expression, and Cellular Localization of a Mouse Cytochrome P450 Highly Expressed in Kidney J. Biol. Chem., June 18, 1999; 274(25): 17777 - 17788. [Abstract] [Full Text] [PDF]
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