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

Involvement of Human Multidrug and Toxin Extrusion 1 in the Drug Interaction between Cimetidine and Metformin in Renal Epithelial Cells

Masahiro Tsuda, Tomohiro Terada, Miki Ueba, Tomoko Sato, Satohiro Masuda, Toshiya Katsura and Ken-ichi Inui
Journal of Pharmacology and Experimental Therapeutics April 2009, 329 (1) 185-191; DOI: https://doi.org/10.1124/jpet.108.147918
Masahiro Tsuda
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tomohiro Terada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Miki Ueba
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tomoko Sato
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Satohiro Masuda
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Toshiya Katsura
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ken-ichi Inui
  • 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

In human proximal tubules, organic cations are taken up from blood into cells by human organic cation transporter 2 [hOCT2/solute carrier (SLC) 22A2] and then eliminated into the lumen by apical H+/organic cation antiporters, human multidrug and toxin extrusion 1 (hMATE1/SLC47A1) and hMATE2-K (SLC47A2). To evaluate drug interactions of cationic drugs in the secretion process, epithelial cells engineered to express both hOCT2 and hMATE transporters are required to simultaneously evaluate drug interactions with renal basolateral and apical organic cation transporters. In the present study, therefore, we assessed the drug interaction between cimetidine and metformin with double-transfected Madin-Darby canine kidney cells stably expressing both hOCT2 and hMATE1 as an in vitro model of the proximal tubular epithelial cells. The basolateral-to-apical transport and intracellular accumulation of [14C]metformin by a double transfectant were markedly inhibited by 1 mM cimetidine at the basolateral side. On the other hand, 1 μM cimetidine at the basolateral side moderately decreased the basolateral-to-apical transport of [14C]metformin and significantly increased the intracellular accumulation of [14C]metformin from the basolateral side, suggesting that cimetidine at a low concentration inhibits apical hMATE1, rather than basolateral hOCT2. Actually, in concentration-dependent inhibition studies by a single transporter expression system, such as human embryonic kidney 293 stably expressing hMATE1, hMATE2-K, or hOCT2, cimetidine showed higher affinity for hMATEs than for hOCT2. These results suggest that apical hMATE1 is involved in drug interactions between cimetidine and cationic compounds in the proximal tubular epithelial cells.

Footnotes

  • This work was supported in part by the Ministry of Health, Labor and Welfare of Japan [Health and Labor Sciences Research Grants]; and the Ministry of Education, Science, Culture and Sports of Japan [Grant-in-aid for Scientific Research].

  • doi:10.1124/jpet.108.147918.

  • ABBREVIATIONS: h, human; OCT, organic cation transporter; SLC, solute carrier; MATE, multidrug and toxin extrusion; MDCK, Madin-Darby canine kidney; TEA, tetraethylammonium; HEK, human embryonic kidney; r, rat.

    • Received October 24, 2008.
    • Accepted January 21, 2009.
  • 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: 329 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 329, Issue 1
1 Apr 2009
  • 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 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.
Involvement of Human Multidrug and Toxin Extrusion 1 in the Drug Interaction between Cimetidine and Metformin in Renal Epithelial Cells
(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

Involvement of Human Multidrug and Toxin Extrusion 1 in the Drug Interaction between Cimetidine and Metformin in Renal Epithelial Cells

Masahiro Tsuda, Tomohiro Terada, Miki Ueba, Tomoko Sato, Satohiro Masuda, Toshiya Katsura and Ken-ichi Inui
Journal of Pharmacology and Experimental Therapeutics April 1, 2009, 329 (1) 185-191; DOI: https://doi.org/10.1124/jpet.108.147918

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

Involvement of Human Multidrug and Toxin Extrusion 1 in the Drug Interaction between Cimetidine and Metformin in Renal Epithelial Cells

Masahiro Tsuda, Tomohiro Terada, Miki Ueba, Tomoko Sato, Satohiro Masuda, Toshiya Katsura and Ken-ichi Inui
Journal of Pharmacology and Experimental Therapeutics April 1, 2009, 329 (1) 185-191; DOI: https://doi.org/10.1124/jpet.108.147918
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

  • 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