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Tissue and cell distribution of the multidrug resistance-associated protein (MRP) in mouse intestine and kidney
1Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 478, Institut Fédératif de Recherche 02, Faculté de Médecine Xavier Bichat, Paris, France.
Abstract:
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 encoded by the MDR gene. Because intestinal and kidney epithelial cells are polarized cells endowed distinct secreting and absorptive ion and protein transport capacities, we investigated the tissue and cell distribution of MRP in adult mouse small intestine, colon, and kidney by immunohistochemistry. Western blot analyses revealed the 190-kD MRP protein in these tissues. MRP was found in the basolateral membranes of intestinal crypt cells, mainly Paneth 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 glomeruli, ascending limb cells, and basolateral membranes of the distal and collecting tubule cells of the kidney but not in proximal tubule cells. Cultured mouse intestinal m-ICcl2 cells and renal distal mpkDCT cells that have retained the features typical of intestinal crypt and renal distal epithelial 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.
Insights
Multidrug resistance-associated protein (MRP) distribution differs from P-glycoprotein in epithelial cells. MRP is localized to basolateral membranes in specific kidney and intestinal cells, suggesting roles in endogenous compound transport.
Area of Science:
- Cell Biology
- Molecular Biology
- Physiology
Background:
- Multidrug resistance-associated protein (MRP) is implicated in drug resistance and substrate export.
- Epithelial cells, like those in the intestine and kidney, are polarized with distinct transport functions.
- The cellular distribution of MRP in these polarized tissues is not well understood.
Purpose of the Study:
- To investigate the tissue and cellular distribution of MRP in adult mouse small intestine, colon, and kidney.
- To compare MRP distribution with that of P-glycoprotein.
- To elucidate the potential role of MRP in epithelial transport.
Main Methods:
- Immunohistochemistry was used to examine MRP localization in tissue sections.
- Western blot analysis confirmed the presence of MRP protein.
- Cultured intestinal and renal epithelial cell lines were used to study MRP in vitro.
Main Results:
- Western blots confirmed a 190-kD MRP protein in intestinal and kidney tissues.
- MRP was detected in the basolateral membranes of intestinal crypt cells (primarily Paneth cells) but not in differentiated enterocytes.
- In the colon, all cells along the crypt-villous axis expressed MRP. In the kidney, MRP was found in glomeruli, ascending limb cells, and distal/collecting tubule cells, but not proximal tubule cells.
- Cultured intestinal and renal epithelial cells also showed basolateral MRP localization.
Conclusions:
- MRP exhibits distinct tissue and subcellular localization patterns in the mouse intestine and kidney.
- The basolateral localization suggests a role for MRP in the transport of endogenous compounds.
- MRP may play a specific role in Paneth cells, renal distal tubule cells, and collecting tubule cells.
