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Expression, Detergent Solubilization, and Purification of a Membrane Transporter, the MexB Multidrug Resistance Protein
10:43

Expression, Detergent Solubilization, and Purification of a Membrane Transporter, the MexB Multidrug Resistance Protein

Published on: December 3, 2010

Basolateral localization and export activity of the human multidrug resistance-associated protein in polarized pig

R Evers1, G J Zaman, L van Deemter

  • 1Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam.

The Journal of Clinical Investigation
|March 1, 1996
PubMed

Insights

The multidrug resistance-associated protein (MRP) transports anticancer drugs and glutathione conjugates out of cells. Inhibitors of MRP may reverse drug resistance, offering new therapeutic strategies.

Area of Science:

  • Cell Biology
  • Pharmacology
  • Molecular Biology

Background:

  • The human multidrug resistance-associated protein (MRP) is known to confer resistance to cytotoxic drugs by reducing intracellular drug concentrations.
  • Emerging evidence suggests MRP also transports glutathione S-conjugates across cell membranes.

Purpose of the Study:

  • To investigate the transport properties of MRP in intact cells.
  • To determine the localization and function of human MRP expressed in a polarized epithelial cell line.

Main Methods:

  • Human MRP cDNA was expressed in the polarized pig kidney epithelial cell line LLC-PK1.
  • Immunocytochemistry using confocal laser scanning and electron microscopy was employed to determine MRP localization.
  • Transport assays were conducted to measure the movement of glutathione S-conjugates and daunorubicin.

Main Results:

  • MRP was primarily localized to the basolateral plasma membrane of LLC-PK1 cells, not the apical membrane.
  • MRP expression led to increased basolateral transport of S-(2,4-dinitrophenyl)-glutathione and daunorubicin.
  • Sulfinpyrazone and probenecid inhibited MRP-mediated basolateral transport but not MDR1 P-glycoprotein-mediated apical transport.

Conclusions:

  • MRP functions as a basolateral transporter of glutathione S-conjugates and anticancer drugs in polarized epithelial cells.
  • Inhibitors like probenecid and sulfinpyrazone show potential for developing MRP-specific drug resistance reversal agents.
  • Understanding MRP localization and function is crucial for designing targeted cancer therapies.

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