Expression and localization of multidrug resistant protein mrp2 in rat small intestine.
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.
Mottino
A D
AD
Graduate Center for Toxicology, University of Kentucky, Lexington 40536-0305, USA.
Hoffman
T
T
Jennes
L
L
Vore
M
M
D018528:ATP-Binding Cassette Transporters / Q000032:analysis* / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D018432:Drug Resistance, Multiple; D005260:Female; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000737:chemistry*; D008871:Microvilli / Q000737:chemistry; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D018528:ATP-Binding Cassette Transporters; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger