Multidrug-resistance protein 5 is a multispecific organic anion transporter able to transport nucleotide analogs.

Article Details

Citation

Copy to clipboard

Wijnholds J, Mol CA, van Deemter L, de Haas M, Scheffer GL, Baas F, Beijnen JH, Scheper RJ, Hatse S, De Clercq E, Balzarini J, Borst P

Multidrug-resistance protein 5 is a multispecific organic anion transporter able to transport nucleotide analogs.

Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7476-81.

PubMed ID

10840050 [ View in PubMed

]

Abstract

Two prominent members of the ATP-binding cassette superfamily of transmembrane proteins, multidrug resistance 1 (MDR1) P-glycoprotein and multidrug resistance protein 1 (MRP1), can mediate the cellular extrusion of xenobiotics and (anticancer) drugs from normal and tumor cells. The MRP subfamily consists of at least six members, and here we report the functional characterization of human MRP5. We found resistance against the thiopurine anticancer drugs, 6-mercaptopurine (6-MP) and thioguanine, and the anti-HIV drug 9-(2-phosphonylmethoxyethyl)adenine (PMEA) in MRP5-transfected cells. This resistance is due to an increased extrusion of PMEA and 6-thioinosine monophosphate from the cells that overproduce MRP5. In polarized Madin-Darby canine kidney II (MDCKII) cells transfected with an MRP5 cDNA construct, MRP5 is routed to the basolateral membrane and these cells transport S-(2,4-dinitrophenyl)glutathione and glutathione preferentially toward the basal compartment. Inhibitors of organic anion transport inhibit transport mediated by MRP5. We speculate that MRP5 might play a role in some cases of unexplained resistance to thiopurines in acute lymphoblastic leukemia and/or to antiretroviral nucleoside analogs in HIV-infected patients.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Adefovir dipivoxil	Multidrug resistance-associated protein 5	Protein	Humans	Unknown	Substrate	Details
Mercaptopurine	Multidrug resistance-associated protein 5	Protein	Humans	Unknown	Substrate	Details
Sulfinpyrazone	Multidrug resistance-associated protein 5	Protein	Humans	Unknown	Inhibitor	Details

Polypeptides

Name	UniProt ID
Multidrug resistance-associated protein 5	O15440	Details