FEBS Letters
Volume 580, Issue 4 , Pages 1085-1093, 13 February 2006

On the putative co-transport of drugs by multidrug resistance proteins

Edited by Gerrit van Meer

  • P. Borst

      Affiliations

    • Center of Biomedical Genetics, Division of Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    • Corresponding Author InformationCorresponding author. Fax: +31 20 669 1383.
    • ,
  • N. Zelcer

      Affiliations

    • Howard Hughes Medical Institute, Department of Pathology and Laboratory Medicine, University of California, MacDonald Research Laboratories 4-726, 675 Charles E. Young Drive South, Los Angeles, CA 90095-1662, USA
    • ,
  • K. van de Wetering

      Affiliations

    • Center of Biomedical Genetics, Division of Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    • ,
  • B. Poolman

      Affiliations

    • Department of Biochemistry Groningen Biomolecular Sciences and Biotechnology Institute (GBB), Materials Science Centre (MSC), Nijenborgh 4, 9747 AG Groningen, The Netherlands

Received 3 November 2005; received in revised form 9 December 2005; accepted 13 December 2005. published online 16 December 2005.

Abstract 

Experiments with multidrug resistance-associated protein 1 (MRP1) showed 10-years ago that transport of vincristine (VCR) by MRP1 could be stimulated by GSH, and transport of GSH by VCR. Since then many examples of stimulated transport have been reported for MRP1, 2, 3, 4 and 8. We discuss here three models to explain stimulated transport. We favour a model in which a large promiscuous binding site can bind more than one ligand, allowing cooperative/competitive interactions between ligands within the binding site. We conclude that there is no unambiguous proof for co-transport of two different ligands by MRPs, but that cross-stimulated transport can explain the published data.

Keywords: ABC transporters, Homotropic cooperativity, Heterotropic cooperativity, Transport kinetics, MRPs

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PII: S0014-5793(05)01508-5

doi:10.1016/j.febslet.2005.12.039

FEBS Letters
Volume 580, Issue 4 , Pages 1085-1093, 13 February 2006

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