Send to

Choose Destination
See comment in PubMed Commons below
Mol Pharmacol. 2003 Feb;63(2):351-8.

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

Author information

  • 1Medical Sciences Division, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.


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.

[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk