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Vol. 293, Issue 3, 717-723, June 2000
Graduate Center for Toxicology (A.D.M., T.H., M.V.) and Department
of Anatomy and Neurobiology (L.J.), University of Kentucky,
Lexington, Kentucky
The expression of multidrug resistance-associated protein isoform 2 (mrp2), the ATP-dependent export pump that mediates the transport of glucuronic acid-, glutathione-, and sulfate-conjugated derivatives, was studied in rat small intestine. The small intestine was divided into nine equal segments, and mrp2 content was analyzed in
homogenate and brush border membrane preparations by Western analysis. mrp2 protein was present mainly in brush border
membrane of the proximal segments and gradually decreased from jejunum to the distal ileum. We also analyzed the content of mrp2 in
three different populations of proximal enterocytes obtained from the upper and lower villus and the crypt regions. The export pump was
mainly expressed in the villus cells and to a lesser degree in the
crypt cells of the epithelium. Immunohistochemical analysis performed
in duodenum, jejunum, and ileum confirmed in situ the Western blot
findings. Analysis of mRNA encoding mrp2 in proximal and distal
segments revealed a similar content in both regions, whereas
distribution along the villus-crypt axis was similar to the protein
gradient. Because conjugating enzymes are distributed similarly to
mrp2, we conclude that they may act coordinately to contribute to
first-pass metabolism of drugs and other xenobiotics in the proximal
small intestine.
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