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

P Borst*, N Zelcer, K van de Wetering, B Poolman

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

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Abstract

Experiments with multidrug resistance-associated protein I (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.

(c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)1085-1093
Number of pages9
JournalFEBS Letters
Volume580
Issue number4
DOIs
Publication statusPublished - 13-Feb-2006

Keywords

  • ABC transporters
  • homotropic cooperativity
  • heterotropic cooperativity
  • transport kinetics
  • MRPs
  • REDUCED GLUTATHIONE
  • LEUKOTRIENE C-4
  • VINCRISTINE TRANSPORT
  • CYTOCHROME-P450 3A4
  • CRYSTAL-STRUCTURES
  • ABC TRANSPORTERS
  • ORGANIC-ANIONS
  • BINDING SITES
  • MRP4 ABCC4
  • BILE-ACIDS

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