Characterization of the transport properties of human multidrug resistance protein 7 (MRP7, ABCC10).

Article Details

Citation

Chen ZS, Hopper-Borge E, Belinsky MG, Shchaveleva I, Kotova E, Kruh GD

Characterization of the transport properties of human multidrug resistance protein 7 (MRP7, ABCC10).

Mol Pharmacol. 2003 Feb;63(2):351-8.

PubMed ID
12527806 [ View in PubMed
]
Abstract

Human multidrug resistance protein 7 (MRP7, ABCC10) is a recently described member of the C family of ATP binding cassette proteins (Cancer Lett 162:181-191, 2001). However, neither its biochemical activity nor physiological functions have been determined. Here we report the results of investigations of the in vitro transport properties of MRP7 using membrane vesicles prepared from human embryonic kidney 293 cells transfected with MRP7 expression vector. It is shown that expression of MRP7 is specifically associated with the MgATP-dependent transport of 17beta-estradiol-(17-beta-D-glucuronide) (E(2)17betaG). E(2)17betaG transport was saturable, with K(m) and V(max) values of 57.8 +/- 15 microM and 53.1 +/- 20 pmol/mg/min. By contrast, with E(2)17betaG, only modest enhancement of LTC(4) transport was observed and transport of several other established substrates of MRP family transporters was not detectable to any extent. In accord with the notion that MRP7 has a bipartite substrate binding pocket composed of sites for anionic and lipophilic moieties, transport of E(2)17betaG was susceptible to competitive inhibition by both amphiphiles, such as leukotriene C(4) (K(i(app)), 1.5 microM), glycolithocholate 3-sulfate (K(i(app)), 34.2 microM) and MK571 (K(i(app)), 28.5 microM), and lipophilic agents such as cyclosporine A (K(i(app)), 14.4 microM). Of the inhibitors tested, LTC(4) was the most potent, in agreement with the possibility that it is a substrate of the pump. The determination that MRP7 has the facility for mediating the transport of conjugates such as E(2)17betaG indicates that it is a lipophilic anion transporter involved in phase III (cellular extrusion) of detoxification.

DrugBank Data that Cites this Article

Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
CyclosporineMultidrug resistance-associated protein 7ProteinHumans
Unknown
Substrate
Inhibitor
Details
DoxorubicinMultidrug resistance-associated protein 7ProteinHumans
Unknown
Inhibitor
Details
EstradiolMultidrug resistance-associated protein 7ProteinHumans
Unknown
Inhibitor
Details
Estradiol acetateMultidrug resistance-associated protein 7ProteinHumans
Unknown
Inhibitor
Details
Estradiol benzoateMultidrug resistance-associated protein 7ProteinHumans
Unknown
Inhibitor
Details
Estradiol cypionateMultidrug resistance-associated protein 7ProteinHumans
Unknown
Inhibitor
Details
Estradiol dienanthateMultidrug resistance-associated protein 7ProteinHumans
Unknown
Inhibitor
Details
Estradiol valerateMultidrug resistance-associated protein 7ProteinHumans
Unknown
Inhibitor
Details
EtoposideMultidrug resistance-associated protein 7ProteinHumans
Unknown
Substrate
Inhibitor
Details
MethotrexateMultidrug resistance-associated protein 7ProteinHumans
Unknown
Inhibitor
Details
PaclitaxelMultidrug resistance-associated protein 7ProteinHumans
Unknown
Substrate
Inhibitor
Details
SildenafilMultidrug resistance-associated protein 7ProteinHumans
Unknown
Inhibitor
Details
SulfinpyrazoneMultidrug resistance-associated protein 6ProteinHumans
Unknown
Inhibitor
Details
Taurocholic acidMultidrug resistance-associated protein 7ProteinHumans
Unknown
Inhibitor
Details
VerapamilMultidrug resistance-associated protein 7ProteinHumans
Unknown
Inhibitor
Details
VincristineMultidrug resistance-associated protein 7ProteinHumans
Unknown
Substrate
Inhibitor
Details
Polypeptides
NameUniProt ID
Multidrug resistance-associated protein 7Q5T3U5Details