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.