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

@article{Wijnholds2000MultidrugresistanceP5,
  title={Multidrug-resistance protein 5 is a multispecific organic anion transporter able to transport nucleotide analogs.},
  author={Jan Wijnholds and C A Mol and Liesbeth van Deemter and Marcel de Haas and George L. Scheffer and Frank Baas and Jos H. Beijnen and Rik J. Scheper and Sigrid Hatse and Erik De Clercq and Jan Balzarini and Piet Borst},
  journal={Proceedings of the National Academy of Sciences of the United States of America},
  year={2000},
  volume={97 13},
  pages={
          7476-81
        }
}
  • J. WijnholdsC. Mol P. Borst
  • Published 20 June 2000
  • Biology, Chemistry
  • Proceedings of the National Academy of Sciences of the United States of America
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… 

Figures and Tables from this paper

A family of drug transporters: the multidrug resistance-associated proteins.

Whether long-term inhibition of MRPs in humans can be tolerated (assuming that suitable inhibitors will be found) remains to be determined.

Characterization of Drug Transport by the Human Multidrug Resistance Protein 3 (ABCC3)*

The resistance to etoposide was associated with reduced cellular accumulation and enhanced efflux of this drug and was not affected by depleting cells of glutathione but was inhibited by several common organic anion transport inhibitors.

Characterization of the drug resistance and transport properties of multidrug resistance protein 6 (MRP6, ABCC6).

It is shown that expression of MRP6 is specifically associated with the MgATP-dependent transport of the glutathione S-conjugates leukotriene C(4) and S-(2, 4-dinitrophenyl)glutathione and the cyclopentapeptide BQ123 but not glucuronate conjugates such as 17beta-estradiol 17-(beta-D-glucuronide).

Role of MRP4 and MRP5 in biology and chemotherapy

Cumulatively, these studies reveal that the ATP-binding cassette (ABC) transporters MRP4 and MRP5 have a unique role in biology and in chemotherapeutic response.

Multidrug resistance proteins (MRPs, ABCCs): importance for pathophysiology and drug therapy.

  • D. Keppler
  • Biology, Medicine
    Handbook of experimental pharmacology
  • 2011
The role of MRP subfamily members in pathophysiology may be illustrated by the MRP-mediated release of proinflammatory and immunomodulatory mediators such as leukotrienes and prostanoids.

The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs

  • G. ReidP. Wielinga P. Borst
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2003
Investigation of the interaction between prostaglandins and members of the ATP-binding cassette (ABC) transporter ABCC [multidrug resistance protein (MRP)] family of membrane export pumps suggests that MRP4 can release prostaglandsins from cells, and that some nonsteroidal antiinflammatory drugs might also act by inhibiting this release.

Cellular Export of Drugs and Signaling Molecules by the ATP-binding Cassette Transporters MRP4 (ABCC4) and MRP5 (ABCC5)

Tissue distribution and subcellular localization of MRP4 and MRP5 specifically in smooth muscle cells, platelet-dense granules, and nervous cells, point not only to a possible function of these transporters as exporters in cellular defense, but also to a physiological function in signaling processes.

The Multidrug Resistance Protein 5 Functions as an ATP-dependent Export Pump for Cyclic Nucleotides*

Evidence is provided that cyclic nucleotides are physiological substrates for MRP5 and may represent a novel pharmacological target for the enhancement of tissue levels of cGMP.

Role of glutathione in the multidrug resistance protein 4 (MRP4/ABCC4)-mediated efflux of cAMP and resistance to purine analogues.

It is concluded that as well as nucleotide and nucleoside analogues, ABCC4 can mediate the export of GSH and mediates resistance to purine analogues 9-(2-phosphonylmethoxyethyl)-adenine and 6-thioguanine.

Transmembrane transport of endo- and xenobiotics by mammalian ATP-binding cassette multidrug resistance proteins.

What is known of the structure of the MRPs and the mechanisms by which they recognize and transport their diverse substrates are described and evidence that they may be involved in the clinical drug resistance of various forms of cancer is summarized.
...

References

SHOWING 1-10 OF 53 REFERENCES

Expression of multidrug resistance protein-3 (multispecific organic anion transporter-D) in human embryonic kidney 293 cells confers resistance to anticancer agents.

Results indicate that MRP3 confers resistance to some anticancer agents but that its resistance pattern is distinct from the resistance patterns of other ABC transporters involved in resistance to natural product chemotherapeutic agents.

MRP3, an organic anion transporter able to transport anti-cancer drugs.

MRP3 is an organic anion and multidrug transporter, like the GS-X pumps MRP1 and MRP2, and in Madin-Darby canine kidney II cells, MRP3 routes to the basolateral membrane and mediates transport of the organicAnion S-(2,4-dinitrophenyl-)glutathione toward the basoliateral side of the monolayer.

Evidence that the multidrug resistance protein (MRP) functions as a co-transporter of glutathione and natural product toxins.

Observations provide evidence that baseline MRP expression protects cells from the toxic effects of xenobiotics by effluxing the xenobiotic and GSH from the intracellular compartment into the extracellular medium by a co-transport mechanism and disruption of the gene encoding MRP abrogates the cotransport of Xenobiotics and G SH.

Drug resistance and ATP-dependent conjugate transport mediated by the apical multidrug resistance protein, MRP2, permanently expressed in human and canine cells.

The cloned MRP2 (symbol ABCC2), a MRP family member localized to the apical membrane of polarized cells, demonstrates that MRP 2 confers resistance to cytotoxic drugs.

ATP-dependent Transport of Bile Salts by Rat Multidrug Resistance-associated Protein 3 (Mrp3)*

The involvement of Mrp3 in the transport of endogenous bile salts was investigated and the finding that MRP3 is extensively expressed on the basolateral membrane of human cholangiocytes, suggests that MRp3/Mrp3 plays a significant role in the cholehepatic circulation of bile salt.

Drug export activity of the human canalicular multispecific organic anion transporter in polarized kidney MDCK cells expressing cMOAT (MRP2) cDNA.

It is shown that cMOAT causes transport of the organic anions S-(2,4-dinitrophenyl)-glutathione, the glutathione conjugate of ethacrynic acid, and S-(PGA1)-gluten, a substrate not shown to be transported by organic anion transporters previously.

Multidrug resistance protein (MRP)-mediated transport of leukotriene C4 and chemotherapeutic agents in membrane vesicles. Demonstration of glutathione-dependent vincristine transport.

Evidence is provided of the ability of MRP to transport cysteinyl leukotriene C4 in membrane vesicles from MRP-transfected HeLa cells (T14), as well as drug-selected H69AR lung cancer cells which express high levels of MRp.
...