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 ArticleMetabolism, Transport, and Pharmacogenomics

Effects of β-Blockers and Tricyclic Antidepressants on the Activity of Human Organic Anion Transporting Polypeptide 1A2 (OATP1A2)

Jennifer Lu, Veronique Michaud, Liliam Gabriela Guilarte Moya, Fleur Gaudette, Yat Hei Leung and Jacques Turgeon
Journal of Pharmacology and Experimental Therapeutics March 2015, 352 (3) 552-558; DOI: https://doi.org/10.1124/jpet.114.219287
Jennifer Lu
Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), Montreal, Quebec, Canada (J.L., V.M., L.G.G.M., F.G., Y.H.L., J.T.); and Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada (J.L., V.M., L.G.G.M., Y.H.L., J.T.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Veronique Michaud
Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), Montreal, Quebec, Canada (J.L., V.M., L.G.G.M., F.G., Y.H.L., J.T.); and Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada (J.L., V.M., L.G.G.M., Y.H.L., J.T.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Liliam Gabriela Guilarte Moya
Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), Montreal, Quebec, Canada (J.L., V.M., L.G.G.M., F.G., Y.H.L., J.T.); and Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada (J.L., V.M., L.G.G.M., Y.H.L., J.T.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Fleur Gaudette
Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), Montreal, Quebec, Canada (J.L., V.M., L.G.G.M., F.G., Y.H.L., J.T.); and Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada (J.L., V.M., L.G.G.M., Y.H.L., J.T.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yat Hei Leung
Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), Montreal, Quebec, Canada (J.L., V.M., L.G.G.M., F.G., Y.H.L., J.T.); and Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada (J.L., V.M., L.G.G.M., Y.H.L., J.T.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jacques Turgeon
Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), Montreal, Quebec, Canada (J.L., V.M., L.G.G.M., F.G., Y.H.L., J.T.); and Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada (J.L., V.M., L.G.G.M., Y.H.L., J.T.)
  • 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 + SI
  • PDF
Loading

Abstract

The organic anion transporting polypeptide 1A2 (OATP1A2), a membrane drug transporter expressed on important organs (such as the brain, kidney, and intestine) may be a key element in the disposition of drugs. Previous studies demonstrated that it could transport a broad spectrum of substrates, including endogenous molecules and clinically relevant drugs, such as several β-blockers and 3-hydroxy-3-methylglutaryl–CoA reductase inhibitors. The primary objective of this study was to investigate OATP1A2 transport activity using rosuvastatin as a probe substrate and evaluate competitive inhibition of its transport by β-blockers. Rosuvastatin transport was saturable, with a Km of 60.2 µM. With the exception of carvedilol (IC50 of 3.2 µM), all of the other β-blockers that were evaluated had a small or insignificant effect on OATP1A2-mediated uptake of rosuvastatin. Carvedilol differs from the other β-blockers by the tricyclic moiety in its chemical structure. As a secondary objective, the transport of a series of tricyclic compounds by OATP1A2 and their potential for rosuvastatin transport inhibition were evaluated. Tricyclic compounds were not OATP1A2 substrates. On the other hand, tricyclic compounds with a short aliphatic amine chain inhibited OATP1A2-mediated rosuvastatin transport. Our data suggest that these drugs may modulate the transport of OATP1A2 substrates and may affect drug actions.

Footnotes

    • Received August 20, 2014.
    • Accepted January 5, 2015.
  • This work was supported by the Fonds de Recherche Santé Québec (FRSQ) and internal funding obtained from the Fondation du CHUM. J.L. and Y.H.L. are the recipients of a studentship from the Fonds de la Recherche du Québec en Santé (FRQS). V.M. is the recipient of a research scholarship from FRQS in partnership with the Institut national d’excellence en santé et en services sociaux (INESSS).

  • dx.doi.org/10.1124/jpet.114.219287.

  • ↵Embedded ImageThis article has supplemental material available at jpet.aspetjournals.org.

  • Copyright © 2015 by 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: 352 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 352, Issue 3
1 Mar 2015
  • 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 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.
Effects of β-Blockers and Tricyclic Antidepressants on the Activity of Human Organic Anion Transporting Polypeptide 1A2 (OATP1A2)
(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 ArticleMetabolism, Transport, and Pharmacogenomics

OATP1A2 Block by β-Blockers and Tricyclic Antidepressants

Jennifer Lu, Veronique Michaud, Liliam Gabriela Guilarte Moya, Fleur Gaudette, Yat Hei Leung and Jacques Turgeon
Journal of Pharmacology and Experimental Therapeutics March 1, 2015, 352 (3) 552-558; DOI: https://doi.org/10.1124/jpet.114.219287

Citation Manager Formats

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

Share
Research ArticleMetabolism, Transport, and Pharmacogenomics

OATP1A2 Block by β-Blockers and Tricyclic Antidepressants

Jennifer Lu, Veronique Michaud, Liliam Gabriela Guilarte Moya, Fleur Gaudette, Yat Hei Leung and Jacques Turgeon
Journal of Pharmacology and Experimental Therapeutics March 1, 2015, 352 (3) 552-558; DOI: https://doi.org/10.1124/jpet.114.219287
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • HDL Mimetic 4F Modulates Aβ Distribution in Brain and Plasma
  • AOX1 Inhibition by Gefitinib, Erlotinib, and Metabolites
  • Catalytic Activity of CYP2C9 Variants
Show more Metabolism, Transport, and Pharmacogenomics

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