CYP2J SUBFAMILY CYTOCHROME P450S IN THE GASTROINTESTINAL-TRACT - EXPRESSION, LOCALIZATION, AND POTENTIAL FUNCTIONAL-SIGNIFICANCE

Our laboratory recently described a new human cytochrome P450 arachido nic acid epoxygenase (CYP2J2) and the corresponding rat homologue (CYP 2J3), both of which were expressed in extrahepatic tissues. Northern a nalysis of RNA prepared from the human and rat intestine demonstrated that CYP2J2 and CYP2J3 mRNAs were expressed primarily in the small int estine and colon. In contrast, immunoblotting studies using a polyclon al antibody raised against recombinant CYP2J2 showed that CYP2J protei ns were expressed throughout the gastrointestinal tract. Immunohistoch emical staining of formalin-fixed, paraffin-embedded intestinal sectio ns using anti-CYP2J2 IgG and avidin-biotin-peroxidase detection reveal ed that CYP2J proteins were present at high levels in nerve cells of a utonomic ganglia, epithelial cells, intestinal smooth muscle cells, an d vascular endothelium. The distribution of this immunoreactivity was confirmed by in situ hybridization using a CYP2J2-specific antisense R NA probe. Microsomal fractions prepared from human jejunum catalyzed t he NADPH-dependent metabolism of arachidonic acid to epoxyeicosatrieno ic acids as the principal reaction products. Direct evidence for the i n vivo epoxidation of arachidonic acid by intestinal cytochrome P450 w as provided by documenting, for the first time, the presence of epoxye icosatrienoic acids in human jejunum by gas chromatography/mass spectr ometry. We conclude that human and rat intestine contain an arachidoni c acid epoxygenase belonging to the CYP2J subfamily that is localized to autonomic ganglion cells, epithelial cells, smooth muscle cells, an d vascular endothelium. in addition to the known effects on intestinal vascular tone, we speculate that CYP2J products may be involved in th e release of intestinal neuropeptides, control of intestinal motility, and/or modulation of intestinal fluid/electrolyte transport.