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
Journal of Pharmacology and Experimental Therapeutics
  • 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
Journal of Pharmacology and Experimental Therapeutics

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 jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleArticle

Polyspecific Organic Anion Transporting Polypeptides Mediate Hepatic Uptake of Amphipathic Type II Organic Cations

Jessica E. van Montfoort, Bruno Hagenbuch, Karin E. Fattinger, Michael Müller, Geny M. M. Groothuis, Dirk K. F. Meijer and Peter J. Meier
Journal of Pharmacology and Experimental Therapeutics October 1999, 291 (1) 147-152;
Jessica E. van Montfoort
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bruno Hagenbuch
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Karin E. Fattinger
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael Müller
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Geny M. M. Groothuis
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dirk K. F. Meijer
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Peter J. Meier
  • 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

Hepatic uptake of albumin-bound amphipathic organic cations has been suggested to be mediated by multispecific bile salt and organic anion transport systems. Therefore, we investigated whether the recently cloned rat organic anion transporting polypeptides 1 and 2 as well as the human organic anion transporting polypeptide might be involved in the hepatocellular uptake of bulky type II organic cations. In cRNA-injected Xenopus laevis oocytes, all three carriers mediated uptake of the known type II model compoundsN-(4,4-azo-n-pentyl)-21-deoxy-ajmalinium and rocuronium, whereas the newly synthesized type II model compoundsN-methyl-quinine and N-methyl-quinidine were transported only by the human organic anion transporting polypeptide. This carrier-mediated uptake ofN-methyl-quinine and N-methyl-quinidine was sodium-independent and saturable with apparentKm values of ∼5 and ∼26 μM, respectively. In contrast to bulky type II organic cations, more hydrophilic type I organic cations such as tributylmethylammonium and choline were not transported by any of the organic anion transporting polypeptides. These findings demonstrate that organic anion transporting polypeptides can also mediate hepatocellular uptake of type II organic cations, whereas uptake of small and more water-soluble type I cations is mediated by different transport systems such as the organic cation transporters.

Footnotes

  • Send reprint requests to: Dr. Peter J. Meier-Abt, Division of Clinical Pharmacology and Toxicology, Department of Medicine, University Hospital, CH-8091 Zurich, Switzerland. E-mail:meierabt{at}kpt.unizh.ch

  • ↵1 This work was supported by the Swiss National Science Foundation Grants 3100-045536.95 (P.J.M.), 3100-045677.95 (B.H.), and 3200-052190.97 (K.E.F.), and the Hartmann-Müller Foundation, Zurich. J.E. van M. was supported by an Ubbo Emmius scholarship of the University of Groningen. B.H. is the recipient of a research development award of the Cloetta Foundation Zurich. K.E.F. is a recipient of a SCORE-A clinical research development award of the Swiss National Science Foundation. A preliminary report of this study has been presented at the 49th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Chicago, November 6–10, 1998, and published in abstract form (Hepatology28, 506A, 1998).

  • Abbreviations:
    OCT
    organic cation transporters
    APDA
    N-(4,4-azo-n-pentyl)-21-deoxyajmalinium
    APM
    azidoprocainamide methoiodide
    APQ
    N-(4,4-azo-n-pentyl)-quinuclidine
    OAT
    organic anion transporter
    Oatp1
    rat organic anion transporting polypeptide 1
    Oatp2
    rat organic anion transporting polypeptide 2
    OATP
    human organic anion transporting polypeptide
    TBuMA
    tributylmethylammonium
    • Received March 12, 1999.
    • Accepted May 26, 1999.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET 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

Journal of Pharmacology and Experimental Therapeutics: 291 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 291, Issue 1
1 Oct 1999
  • 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 Journal of Pharmacology and Experimental Therapeutics 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.
Polyspecific Organic Anion Transporting Polypeptides Mediate Hepatic Uptake of Amphipathic Type II Organic Cations
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Polyspecific Organic Anion Transporting Polypeptides Mediate Hepatic Uptake of Amphipathic Type II Organic Cations

Jessica E. van Montfoort, Bruno Hagenbuch, Karin E. Fattinger, Michael Müller, Geny M. M. Groothuis, Dirk K. F. Meijer and Peter J. Meier
Journal of Pharmacology and Experimental Therapeutics October 1, 1999, 291 (1) 147-152;

Citation Manager Formats

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

Share
Research ArticleArticle

Polyspecific Organic Anion Transporting Polypeptides Mediate Hepatic Uptake of Amphipathic Type II Organic Cations

Jessica E. van Montfoort, Bruno Hagenbuch, Karin E. Fattinger, Michael Müller, Geny M. M. Groothuis, Dirk K. F. Meijer and Peter J. Meier
Journal of Pharmacology and Experimental Therapeutics October 1, 1999, 291 (1) 147-152;
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
    • Experimental Procedures
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • PST3093 Stimulates SERCA2a and Improves Cardiac Function
  • CRV431 Decreases Liver Fibrosis and Tumor Development
  • Meeting Report for the ASPET–Ray Fuller Symposium: Cellular Mechanisms and Novel Strategies for Pain Control
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 JPET
  • 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
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

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