Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Molecular Pharmacology
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Molecular Pharmacology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Characterization of the Transport Properties of Human Multidrug Resistance Protein 7 (MRP7, ABCC10)

Zhe-Sheng Chen, Elizabeth Hopper-Borge, Martin G. Belinsky, Irina Shchaveleva, Elena Kotova and Gary D. Kruh
Molecular Pharmacology February 2003, 63 (2) 351-358; DOI: https://doi.org/10.1124/mol.63.2.351
Zhe-Sheng Chen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elizabeth Hopper-Borge
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Martin G. Belinsky
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Irina Shchaveleva
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elena Kotova
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gary D. Kruh
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Human multidrug resistance protein 7 (MRP7, ABCC10) is a recently described member of the C family of ATP binding cassette proteins (Cancer Lett162:181–191, 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 17β-estradiol-(17-β-d-glucuronide) (E217βG). E217βG transport was saturable, with Km andVmax values of 57.8 ± 15 μM and 53.1 ± 20 pmol/mg/min. By contrast, with E217βG, only modest enhancement of LTC4 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 E217βG was susceptible to competitive inhibition by both amphiphiles, such as leukotriene C4(Ki(app), 1.5 μM), glycolithocholate 3-sulfate (Ki(app), 34.2 μM) and MK571 (Ki(app), 28.5 μM), and lipophilic agents such as cyclosporine A (Ki(app), 14.4 μM). Of the inhibitors tested, LTC4 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 E217βG indicates that it is a lipophilic anion transporter involved in phase III (cellular extrusion) of detoxification.

Footnotes

  • This work was supported in part by National Institutes of Health grants CA73728 (to G.D.K.) and CA06927 to the Fox Chase Cancer Center and by an appropriation from the Commonwealth of Pennsylvania. Z.-S.C. is the recipient of a W. J. Avery Fellowship from Fox Chase Cancer Center and a Japan Research Foundation Award for Clinical Pharmacology. E.H.-B. received fellowship support from National Institutes of Health training grant CA75266.

  • Abbreviations:
    MRP
    multidrug resistance protein (MRP1-MRP7, gene symbols ABCC1-ABCC6 and ABCC10)
    MOAT
    multispecific organic anion transporter (MOAT-B, MOAT-C, MOAT-D and MOAT-E are alternative names for MRP4, MRP5, MRP3 and MRP6, respectively, and cMOAT is an alternative name for MRP2)
    LTC4
    leukotriene C4
    DNP-SG, S-(2,4-dinitrophenyl)glutathione
    E217βG, 17β-estradiol 17-(β-d-glucuronide)
    E23SO417βG
    17β-estradiol 3-sulfate-17-(β-d-glucuronide)
    ABC
    ATP-binding cassette
    HEK
    human embryonic kidney
    MK571
    3-([{3-(2-[7-chloro-2-quinolinyl]ethenyl)phenyl}-{(3-dimethyl-amino-3-oxopropyl)-thio}-methyl]thio)propanoic acid
    PSC833
    3-oxo-4-butenyl-4-methyl-(Thr1)-(Val2)-cyclosporin
    • Received June 13, 2002.
    • Accepted November 5, 2002.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Molecular Pharmacology: 63 (2)
Molecular Pharmacology
Vol. 63, Issue 2
1 Feb 2003
  • Table of Contents
  • About the Cover
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Characterization of the Transport Properties of Human Multidrug Resistance Protein 7 (MRP7, ABCC10)
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Characterization of the Transport Properties of Human Multidrug Resistance Protein 7 (MRP7, ABCC10)

Zhe-Sheng Chen, Elizabeth Hopper-Borge, Martin G. Belinsky, Irina Shchaveleva, Elena Kotova and Gary D. Kruh
Molecular Pharmacology February 1, 2003, 63 (2) 351-358; DOI: https://doi.org/10.1124/mol.63.2.351

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

Characterization of the Transport Properties of Human Multidrug Resistance Protein 7 (MRP7, ABCC10)

Zhe-Sheng Chen, Elizabeth Hopper-Borge, Martin G. Belinsky, Irina Shchaveleva, Elena Kotova and Gary D. Kruh
Molecular Pharmacology February 1, 2003, 63 (2) 351-358; DOI: https://doi.org/10.1124/mol.63.2.351
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Analgesic Effects and Mechanisms of Licochalcones
  • Induced Fit Ligand Binding to CYP3A4
  • Englerin A Inhibits T-Type Channels
Show more Article

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Molecular Pharmacology
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics