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
Rapid CommunicationShort Communication

Role of ABCG2 in Transport of the Mammalian Lignan Enterolactone and its Secretion into Milk in Abcg2 Knockout Mice

Verónica Miguel, Jon Andoni Otero, Rocío García-Villalba, Francisco Tomás-Barberán, Juan Carlos Espín, Gracia Merino and Ana I. Álvarez
Drug Metabolism and Disposition May 2014, 42 (5) 943-946; DOI: https://doi.org/10.1124/dmd.113.055970
Verónica Miguel
Department of Biomedical Sciences, Physiology, Veterinary Faculty (V.M., A.I.A., J.A.O., G.M.) and Instituto de Desarrollo Ganadero y Sanidad Animal (J.A.O., G.M.), University of Leon, Leon, Spain; and Research Group on Quality, Safety, and Bioactivity of Plant Foods, Centro de Edafología y Biología Aplicada del Segura, Murcia, Spain (R.G.-V., F.T.-B., J.C.E.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jon Andoni Otero
Department of Biomedical Sciences, Physiology, Veterinary Faculty (V.M., A.I.A., J.A.O., G.M.) and Instituto de Desarrollo Ganadero y Sanidad Animal (J.A.O., G.M.), University of Leon, Leon, Spain; and Research Group on Quality, Safety, and Bioactivity of Plant Foods, Centro de Edafología y Biología Aplicada del Segura, Murcia, Spain (R.G.-V., F.T.-B., J.C.E.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rocío García-Villalba
Department of Biomedical Sciences, Physiology, Veterinary Faculty (V.M., A.I.A., J.A.O., G.M.) and Instituto de Desarrollo Ganadero y Sanidad Animal (J.A.O., G.M.), University of Leon, Leon, Spain; and Research Group on Quality, Safety, and Bioactivity of Plant Foods, Centro de Edafología y Biología Aplicada del Segura, Murcia, Spain (R.G.-V., F.T.-B., J.C.E.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Francisco Tomás-Barberán
Department of Biomedical Sciences, Physiology, Veterinary Faculty (V.M., A.I.A., J.A.O., G.M.) and Instituto de Desarrollo Ganadero y Sanidad Animal (J.A.O., G.M.), University of Leon, Leon, Spain; and Research Group on Quality, Safety, and Bioactivity of Plant Foods, Centro de Edafología y Biología Aplicada del Segura, Murcia, Spain (R.G.-V., F.T.-B., J.C.E.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Juan Carlos Espín
Department of Biomedical Sciences, Physiology, Veterinary Faculty (V.M., A.I.A., J.A.O., G.M.) and Instituto de Desarrollo Ganadero y Sanidad Animal (J.A.O., G.M.), University of Leon, Leon, Spain; and Research Group on Quality, Safety, and Bioactivity of Plant Foods, Centro de Edafología y Biología Aplicada del Segura, Murcia, Spain (R.G.-V., F.T.-B., J.C.E.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gracia Merino
Department of Biomedical Sciences, Physiology, Veterinary Faculty (V.M., A.I.A., J.A.O., G.M.) and Instituto de Desarrollo Ganadero y Sanidad Animal (J.A.O., G.M.), University of Leon, Leon, Spain; and Research Group on Quality, Safety, and Bioactivity of Plant Foods, Centro de Edafología y Biología Aplicada del Segura, Murcia, Spain (R.G.-V., F.T.-B., J.C.E.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ana I. Álvarez
Department of Biomedical Sciences, Physiology, Veterinary Faculty (V.M., A.I.A., J.A.O., G.M.) and Instituto de Desarrollo Ganadero y Sanidad Animal (J.A.O., G.M.), University of Leon, Leon, Spain; and Research Group on Quality, Safety, and Bioactivity of Plant Foods, Centro de Edafología y Biología Aplicada del Segura, Murcia, Spain (R.G.-V., F.T.-B., J.C.E.)
  • 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

Lignans are phytoestrogens that are metabolized by the gut microbiota to enterodiol and enterolactone, the main biologically active enterolignans. Substantial interindividual variation in plasma concentration and urinary excretion of enterolignans has been reported, this being determined, at least in part, by the intake of lignan precursors, the gut microbiota, and the host’s phase 2 conjugating enzyme activity. However, the role of ATP-binding cassette (ABC) transporters in the transport and disposition of enterolactone has not been reported so far. Active transport assays using parental and Madin-Darby canine kidney epithelial cells transduced with murine and human ABCG2 showed a significant increase in apically directed translocation of enterolactone in transduced cells, which was confirmed by using the selective ABCG2 inhibitor Ko143. In addition, enterolactone also inhibited transport of the antineoplastic agent mitoxantrone as a model substrate, with inhibition percentages of almost 40% at 200 μM for human ABCG2. Furthermore, the endogenous levels in plasma and milk of enterolactone in wild-type and Abcg2(−/−) knockout female mice were analyzed. The milk/plasma ratio decreased significantly in the Abcg2(−/−) phenotype, as compared with the wild-type mouse group (0.4 ± 0.1 as against 6.4 ± 2.6). This paper is the first to report that enterolactone is a transported substrate and therefore most probably a competitive inhibitor of ABCG2, which suggests it has a role in the interindividual variations in the disposition of enterolactone and its secretion into milk. The inhibitory activity identified provides a solid basis for further investigation in possible food-drug interactions.

Footnotes

    • Received November 11, 2013.
    • Accepted February 25, 2014.
  • This work was supported by the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund [Projects CICYT AGL2012-31116, AGL2011-22447] and the Seneca Foundation of the Murcia Region, Spain [Excellence Group GERM 06 04486, 05556/PI/04, Consolider Ingenio 2010, CSD2007-00063 (Fun-C-Food)].

  • J.A.O. holds a predoctoral fellowship of the Basque Government and R.G.-V. is the holder of a JAE-DOC contract from the Spanish Higher Council for Scientific Research, cofinanced by the European Social Fund.

  • dx.doi.org/10.1124/dmd.113.055970.

  • Copyright © 2014 by 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: 42 (5)
Drug Metabolism and Disposition
Vol. 42, Issue 5
1 May 2014
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • 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.
Role of ABCG2 in Transport of the Mammalian Lignan Enterolactone and its Secretion into Milk in Abcg2 Knockout Mice
(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
Rapid CommunicationShort Communication

ABCG2 Transports Enterolactone

Verónica Miguel, Jon Andoni Otero, Rocío García-Villalba, Francisco Tomás-Barberán, Juan Carlos Espín, Gracia Merino and Ana I. Álvarez
Drug Metabolism and Disposition May 1, 2014, 42 (5) 943-946; DOI: https://doi.org/10.1124/dmd.113.055970

Citation Manager Formats

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

Share
Rapid CommunicationShort Communication

ABCG2 Transports Enterolactone

Verónica Miguel, Jon Andoni Otero, Rocío García-Villalba, Francisco Tomás-Barberán, Juan Carlos Espín, Gracia Merino and Ana I. Álvarez
Drug Metabolism and Disposition May 1, 2014, 42 (5) 943-946; DOI: https://doi.org/10.1124/dmd.113.055970
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
    • Introduction
    • Materials and Methods
    • Results and Discussion
    • Acknowledgments
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Preincubation Effects on Inhibition of OCT1 by CsA
  • Carbamazepine Metabolite and Hypersensitivity Reactions
  • SULT4A1 Preserves Mitochondrial Function
Show more Short Communications

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