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
Drug Metabolism & Disposition
  • 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
Drug Metabolism & Disposition

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 dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

Interaction of Positional Isomers of Quercetin Glucuronides with the Transporter ABCC2 (cMOAT, MRP2)

Gary Williamson, Isabelle Aeberli, Laurence Miguet, Ziding Zhang, M.-Belen Sanchez, Vanessa Crespy, Denis Barron, Paul Needs, Paul A. Kroon, H. Glavinas, Peter Krajcsi and Martin Grigorov
Drug Metabolism and Disposition August 2007, 35 (8) 1262-1268; DOI: https://doi.org/10.1124/dmd.106.014241
Gary Williamson
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Isabelle Aeberli
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Laurence Miguet
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ziding Zhang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M.-Belen Sanchez
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vanessa Crespy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Denis Barron
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Paul Needs
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Paul A. Kroon
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
H. Glavinas
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Peter Krajcsi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Martin Grigorov
  • 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

The exporter ABCC2 (cMOAT, MRP2) is a membrane-bound protein on the apical side of enterocytes and hepatic biliary vessels that transports leukotriene C4, glutathione, some conjugated bile salts, drugs, xenobiotics, and phytonutrients. The latter class includes quercetin, a bioactive flavonoid found in foods such as onions, apples, tea, and wine. There is no available three-dimensional (3D) structure of ABCC2. We have predicted the 3D structure by in silico modeling, showing that 3-[[3-[2-(7-chloroquinolin-2-yl)vinyl]phenyl]-(2-dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid (MK571) binds most tightly to the putative binding site, and then tested the computational prediction experimentally by measuring interaction with all quercetin monoglucuronides occurring in vivo (quercetin substituted with glucuronic acid at the 3-, 3′-, 4′-, and 7-hydroxyl groups). The 4′-O-β-D-glucuronide is predicted in silico to interact most strongly and the 3-O-β-D-glucuronide most weakly, and this prediction is supported experimentally using binding and competition assays on ABCC2-overexpressing baculovirus-infected Sf9 cells. To test the transport in situ, we examined the effect of two ABCC2 inhibitors, MK571 and cyclosporin A, on the transport into the media of quercetin glucuronides produced intracellularly by Caco2 cells. The inhibitors reduced the amount of all quercetin glucuronides in the media. The results show that the molecular model of ABCC2 agrees well with experimentally determined ABCC2-ligand interactions and, importantly, that the interaction of ABCC2 with quercetin glucuronides is dependent on the position and nature of substitution.

Footnotes

  • Solvo Biotechnology has been supported by Grants FP6-2004-LIFESCI-HEALTH-5; Proposal No. 018961, FP6-2004-LIFESCIHEALTH-5; Proposal No. 518246, FP6, Network of Excellence (BioSim) 005137, and Hungarian Grants GVOP 3.1.1–2004-05-0506/3.0, GVOP 3.1.1–2004-05-0440/3.0, GVOP Munka– 00034/2003, NKFP 1/A-041/04, RET, Debrecen, OTKA T 043141. P.N. and P.A.K. are supported by the Biotechnology and Biological Sciences Research Council, UK. G.W., I.A., L.M., Z.Z., M.B.S., V.C., D.B., and M.G. are, or were, employees of Nestlé SA, Switzerland.

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

  • doi:10.1124/dmd.106.014241.

  • ABBREVIATIONS: ABC, ATP-binding cassette; MRP, multidrug resistance protein; TMD, transmembrane domain; TM, transmembrane; 3D, three-dimensional; MK571, 3-[[3-[2-(7-chloroquinolin-2-yl)vinyl]phenyl]-(2-dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid; HPLC, high-performance liquid chromatography; RMSD, root mean square deviation; UGT, UDP-glucuronosyl transferase.

    • Received December 6, 2006.
    • Accepted May 2, 2007.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

 

DMD 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

Drug Metabolism and Disposition: 35 (8)
Drug Metabolism and Disposition
Vol. 35, Issue 8
1 Aug 2007
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Drug Metabolism & Disposition 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.
Interaction of Positional Isomers of Quercetin Glucuronides with the Transporter ABCC2 (cMOAT, MRP2)
(Your Name) has forwarded a page to you from Drug Metabolism & Disposition
(Your Name) thought you would be interested in this article in Drug Metabolism & Disposition.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Interaction of Positional Isomers of Quercetin Glucuronides with the Transporter ABCC2 (cMOAT, MRP2)

Gary Williamson, Isabelle Aeberli, Laurence Miguet, Ziding Zhang, M.-Belen Sanchez, Vanessa Crespy, Denis Barron, Paul Needs, Paul A. Kroon, H. Glavinas, Peter Krajcsi and Martin Grigorov
Drug Metabolism and Disposition August 1, 2007, 35 (8) 1262-1268; DOI: https://doi.org/10.1124/dmd.106.014241

Citation Manager Formats

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

Share
Research ArticleArticle

Interaction of Positional Isomers of Quercetin Glucuronides with the Transporter ABCC2 (cMOAT, MRP2)

Gary Williamson, Isabelle Aeberli, Laurence Miguet, Ziding Zhang, M.-Belen Sanchez, Vanessa Crespy, Denis Barron, Paul Needs, Paul A. Kroon, H. Glavinas, Peter Krajcsi and Martin Grigorov
Drug Metabolism and Disposition August 1, 2007, 35 (8) 1262-1268; DOI: https://doi.org/10.1124/dmd.106.014241
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google 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

  • New Dog P450 3A98 in Gut
  • TMDD Affects PK of IL-10 Fc-Fusion Proteins
  • In Vitro Models to Study P-gp-Mediated Intestinal DDIs
Show more Articles

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

ASPET's Other Journals

  • Journal of Pharmacology and Experimental Therapeutics
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-009X (Online)

Copyright © 2022 by the American Society for Pharmacology and Experimental Therapeutics