Tissue and cell distribution of the multidrug resistance-associated protein (MRP) in mouse intestine and kidney

The multidrug resistance-associated protein (MRP) that is involved in drug resistance and the export of glutathione-conjugated substrates may not have the same epithelial cell membrane distribution as the P-glycoprotein encod ed by the MDR gene. Because intestinal and kidney epithelial cells are pola rized cells endowed distinct secreting and absorptive ion and protein trans port capacities, we investigated the tissue and cell distribution of MRP in adult mouse small intestine, colon, and kidney by immunohistochemistry. We stern blot analyses revealed the 190-kD MRP protein in these tissues. MRP w as found in the basolateral membranes of intestinal crypt cells, mainly Pan eth cells, but not in differentiated enterocytes. All the cells lining the crypt-villous axis of the colon wall contained MRP. MRP was found in the gl omeruli, ascending limb cells, and basolateral membranes of the distal and collecting tubule cells of the kidney but not in proximal tubule cells. Cul tured mouse intestinal m-ICcl2 cells and renal distal mpkDCT cells that hav e retained the features typical of intestinal crypt and renal distal epithe lial cells, respectively, also possess MRP in their basolateral membranes. The patterns of subcellular and cellular distribution indicate that MRP may have a specific role in the basolateral transport of endogenous compounds in Paneth, renal distal, and collecting tubule cells.