Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • 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
  • 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
    • 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
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Multidrug Resistance Proteins 2 and 3 Provide Alternative Routes for Hepatic Excretion of Morphine-Glucuronides

Koen van de Wetering, Noam Zelcer, Annemieke Kuil, Wouter Feddema, Michel Hillebrand, Maria L. H. Vlaming, Alfred H. Schinkel, Jos H. Beijnen and Piet Borst
Molecular Pharmacology August 2007, 72 (2) 387-394; DOI: https://doi.org/10.1124/mol.107.035592
Koen van de Wetering
Division of Molecular Biology (K.v.d.W., N.Z., A.K., W.F., P.B.) and Division of Experimental Therapy (M.L.H.V., A.H.S.), the Netherlands Cancer Institute, Amsterdam, the Netherlands; and Department of Pharmacy and Pharmacology, Slotervaart Hospital, Amsterdam, the Netherlands (M.H., J.H.B.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Noam Zelcer
Division of Molecular Biology (K.v.d.W., N.Z., A.K., W.F., P.B.) and Division of Experimental Therapy (M.L.H.V., A.H.S.), the Netherlands Cancer Institute, Amsterdam, the Netherlands; and Department of Pharmacy and Pharmacology, Slotervaart Hospital, Amsterdam, the Netherlands (M.H., J.H.B.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Annemieke Kuil
Division of Molecular Biology (K.v.d.W., N.Z., A.K., W.F., P.B.) and Division of Experimental Therapy (M.L.H.V., A.H.S.), the Netherlands Cancer Institute, Amsterdam, the Netherlands; and Department of Pharmacy and Pharmacology, Slotervaart Hospital, Amsterdam, the Netherlands (M.H., J.H.B.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wouter Feddema
Division of Molecular Biology (K.v.d.W., N.Z., A.K., W.F., P.B.) and Division of Experimental Therapy (M.L.H.V., A.H.S.), the Netherlands Cancer Institute, Amsterdam, the Netherlands; and Department of Pharmacy and Pharmacology, Slotervaart Hospital, Amsterdam, the Netherlands (M.H., J.H.B.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michel Hillebrand
Division of Molecular Biology (K.v.d.W., N.Z., A.K., W.F., P.B.) and Division of Experimental Therapy (M.L.H.V., A.H.S.), the Netherlands Cancer Institute, Amsterdam, the Netherlands; and Department of Pharmacy and Pharmacology, Slotervaart Hospital, Amsterdam, the Netherlands (M.H., J.H.B.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maria L. H. Vlaming
Division of Molecular Biology (K.v.d.W., N.Z., A.K., W.F., P.B.) and Division of Experimental Therapy (M.L.H.V., A.H.S.), the Netherlands Cancer Institute, Amsterdam, the Netherlands; and Department of Pharmacy and Pharmacology, Slotervaart Hospital, Amsterdam, the Netherlands (M.H., J.H.B.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alfred H. Schinkel
Division of Molecular Biology (K.v.d.W., N.Z., A.K., W.F., P.B.) and Division of Experimental Therapy (M.L.H.V., A.H.S.), the Netherlands Cancer Institute, Amsterdam, the Netherlands; and Department of Pharmacy and Pharmacology, Slotervaart Hospital, Amsterdam, the Netherlands (M.H., J.H.B.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jos H. Beijnen
Division of Molecular Biology (K.v.d.W., N.Z., A.K., W.F., P.B.) and Division of Experimental Therapy (M.L.H.V., A.H.S.), the Netherlands Cancer Institute, Amsterdam, the Netherlands; and Department of Pharmacy and Pharmacology, Slotervaart Hospital, Amsterdam, the Netherlands (M.H., J.H.B.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Piet Borst
Division of Molecular Biology (K.v.d.W., N.Z., A.K., W.F., P.B.) and Division of Experimental Therapy (M.L.H.V., A.H.S.), the Netherlands Cancer Institute, Amsterdam, the Netherlands; and Department of Pharmacy and Pharmacology, Slotervaart Hospital, Amsterdam, the Netherlands (M.H., J.H.B.)
  • 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

Glucuronidation is a major hepatic detoxification pathway for endogenous and exogenous compounds, resulting in the intracellular formation of polar metabolites that require specialized transporters for elimination. Multidrug resistance proteins (MRPs) are expressed in the liver and can transport glucuronosyl-conjugates. Using morphine as a model aglycone, we demonstrate that morphine-3-glucuronide (M3G), the predominant metabolite, is transported in vitro by human MRP2 (ABCC2), a protein present in the apical membrane of hepatocytes. Loss of biliary M3G secretion in Mrp2(-/-) mice results in its increased sinusoidal transport that can be attributed to Mrp3. Combined loss of Mrp2 and Mrp3 leads to a substantial accumulation of M3G in the liver, from which it is transported across the sinusoidal membrane at a low rate, resulting in the prolonged presence of M3G in plasma. Our results show that murine Mrp2 and Mrp3 provide alternative routes for the excretion of a glucuronidated substrate from the liver in vivo.

  • 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: 72 (2)
Molecular Pharmacology
Vol. 72, Issue 2
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 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.
Multidrug Resistance Proteins 2 and 3 Provide Alternative Routes for Hepatic Excretion of Morphine-Glucuronides
(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

Multidrug Resistance Proteins 2 and 3 Provide Alternative Routes for Hepatic Excretion of Morphine-Glucuronides

Koen van de Wetering, Noam Zelcer, Annemieke Kuil, Wouter Feddema, Michel Hillebrand, Maria L. H. Vlaming, Alfred H. Schinkel, Jos H. Beijnen and Piet Borst
Molecular Pharmacology August 1, 2007, 72 (2) 387-394; DOI: https://doi.org/10.1124/mol.107.035592

Citation Manager Formats

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

Multidrug Resistance Proteins 2 and 3 Provide Alternative Routes for Hepatic Excretion of Morphine-Glucuronides

Koen van de Wetering, Noam Zelcer, Annemieke Kuil, Wouter Feddema, Michel Hillebrand, Maria L. H. Vlaming, Alfred H. Schinkel, Jos H. Beijnen and Piet Borst
Molecular Pharmacology August 1, 2007, 72 (2) 387-394; DOI: https://doi.org/10.1124/mol.107.035592
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike 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

  • GABAAR Molecular Identity in Oligodendrocytes
  • Editing TOP2α Intron-19 5′ SS Circumvents Drug Resistance
  • SerpinA3N and drug induced liver injury
Show more Articles

Similar Articles

  • 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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics