On the putative co-transport of drugs by multidrug resistance proteins.
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.
Borst
P
P
Center of Biomedical Genetics, Division of Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. p.borst@nki.nl
Zelcer
N
N
van de Wetering
K
K
Poolman
B
B
D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*
D027425:ATP-Binding Cassette, Sub-Family C Proteins; D004364:Pharmaceutical Preparations