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

P Borst; N Zelcer; K van de Wetering; B Poolman

doi:10.1016/j.febslet.2005.12.039

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

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

^*Corresponding author voor dit werk

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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.

Originele taal-2	English
Pagina's (van-tot)	1085-1093
Aantal pagina's	9
Tijdschrift	FEBS Letters
Volume	580
Nummer van het tijdschrift	4
DOI's	https://doi.org/10.1016/j.febslet.2005.12.039
Status	Published - 13-feb.-2006

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@article{488ebefca40e41b2bc680e8bf0093aad,

title = "On the putative co-transport of drugs by multidrug resistance proteins",

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.",

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",

author = "P Borst and N Zelcer and {van de Wetering}, K and B Poolman",

year = "2006",

month = feb,

day = "13",

doi = "10.1016/j.febslet.2005.12.039",

language = "English",

volume = "580",

pages = "1085--1093",

journal = "FEBS Letters",

issn = "0014-5793",

publisher = "Wiley",

number = "4",

}

TY - JOUR

T1 - On the putative co-transport of drugs by multidrug resistance proteins

AU - Borst, P

AU - Zelcer, N

AU - van de Wetering, K

AU - Poolman, B

PY - 2006/2/13

Y1 - 2006/2/13

N2 - 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.

AB - 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.

KW - ABC transporters

KW - homotropic cooperativity

KW - heterotropic cooperativity

KW - transport kinetics

KW - MRPs

KW - REDUCED GLUTATHIONE

KW - LEUKOTRIENE C-4

KW - VINCRISTINE TRANSPORT

KW - CYTOCHROME-P450 3A4

KW - CRYSTAL-STRUCTURES

KW - ABC TRANSPORTERS

KW - ORGANIC-ANIONS

KW - BINDING SITES

KW - MRP4 ABCC4

KW - BILE-ACIDS

U2 - 10.1016/j.febslet.2005.12.039

DO - 10.1016/j.febslet.2005.12.039

M3 - Review article

SN - 0014-5793

VL - 580

SP - 1085

EP - 1093

JO - FEBS Letters

JF - FEBS Letters

IS - 4

ER -

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

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