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 ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Characterization of the Uptake of Organic Anion Transporter (OAT) 1 and OAT3 Substrates by Human Kidney Slices

Yoshitane Nozaki, Hiroyuki Kusuhara, Tsunenori Kondo, Maki Hasegawa, Yoshiyuki Shiroyanagi, Hayakazu Nakazawa, Teruo Okano and Yuichi Sugiyama
Journal of Pharmacology and Experimental Therapeutics April 2007, 321 (1) 362-369; DOI: https://doi.org/10.1124/jpet.106.113076
Yoshitane Nozaki
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hiroyuki Kusuhara
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tsunenori Kondo
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maki Hasegawa
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yoshiyuki Shiroyanagi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hayakazu Nakazawa
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Teruo Okano
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yuichi Sugiyama
  • 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

The activities of renal multispecific organic anion transporters (OATs) 1 and 3 have not been fully evaluated in human kidneys. In the present study, the uptake of some organic anions was characterized in kidney slices from human intact renal cortical tissues: hOAT1 and hOAT3 substrates [p-aminohippurate (PAH) and 2,4-dichlorophenoxyacetate (2,4-D)] and hOAT3 substrates [benzylpenicillin (PCG), dehydroepiandrosterone sulfate (DHEAS), and estrone sulfate (ES)]. Despite large interbatch differences, hOAT1 and hOAT3 mRNA levels correlated well, and there was a good correlation between the uptake of PAH and PCG by kidney slices. The uptake of organic anions by kidney slices was saturable with Km values of 31 to 48 μM for PAH, 0.73 to 4.9 μM for 2,4-D, 14 to 90 μM for PCG, and 9.2 to 11 μM for ES. These parameters were comparable with those for hOAT1 and/or hOAT3. The uptake of DHEAS consists of two saturable components with Km values of 2.2 to 3.9 and 1300 μM, and the Km value of the high-affinity component was close to that for hOAT3. Furthermore, PAH more potently inhibited the uptake of 2,4-D than that of PCG and DHEAS. PCG had a weaker effect on the uptake of PAH and 2,4-D than expected from its Km value. Taken together, it is likely that the uptake of PAH and 2,4-D is due to OAT1, and the uptake of PCG and ES and part of DHEAS uptake are due to OAT3 in human kidney slices. Human kidney slices are useful tools for characterizing the renal uptake of drugs.

Footnotes

  • This work was supported by Health and Labor Sciences Research Grants for Research on Regulatory Science of Pharmaceuticals and Medical Devices from the Ministry of Health, Labor, and Welfare (to Y.Su.), by a Grant-in-Aid for Scientific Research (B) from Japan Society for the Promotion of Science (number KAKENHI 18390046 to H.K.), and by a grant for the 21st Century Center of Excellence program “Strategic Approach to Drug Discovery and Development in Pharmaceutical Sciences” from the Ministry of Education, Culture, Sports, Science, and Technology, Japan (Monbukagakusho).

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

  • doi:10.1124/jpet.106.113076.

  • ABBREVIATIONS: OAT, organic anion transporter; PAH, p-aminohippurate; 2,4-D, 2,4-dichlorophenoxyacetate; PCG, benzylpenicillin; DHEAS, dehydroepiandrosterone sulfate; ES, estrone sulfate; KG, ketoglutarate; PCR, polymerase chain reaction; GAPDH, glyceraldehyde-3-phosphate dehydrogenase.

    • Received August 27, 2006.
    • Accepted January 23, 2007.
  • 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.
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 385 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 385, Issue 1
1 Apr 2023
  • 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.
Characterization of the Uptake of Organic Anion Transporter (OAT) 1 and OAT3 Substrates by Human Kidney Slices
(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 ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Characterization of the Uptake of Organic Anion Transporter (OAT) 1 and OAT3 Substrates by Human Kidney Slices

Yoshitane Nozaki, Hiroyuki Kusuhara, Tsunenori Kondo, Maki Hasegawa, Yoshiyuki Shiroyanagi, Hayakazu Nakazawa, Teruo Okano and Yuichi Sugiyama
Journal of Pharmacology and Experimental Therapeutics April 1, 2007, 321 (1) 362-369; DOI: https://doi.org/10.1124/jpet.106.113076

Citation Manager Formats

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

Share
Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Characterization of the Uptake of Organic Anion Transporter (OAT) 1 and OAT3 Substrates by Human Kidney Slices

Yoshitane Nozaki, Hiroyuki Kusuhara, Tsunenori Kondo, Maki Hasegawa, Yoshiyuki Shiroyanagi, Hayakazu Nakazawa, Teruo Okano and Yuichi Sugiyama
Journal of Pharmacology and Experimental Therapeutics April 1, 2007, 321 (1) 362-369; DOI: https://doi.org/10.1124/jpet.106.113076
Reddit logo Twitter logo Facebook 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

  • MIP3α in Progressive Renal Injury Associated with Obesity
  • A Novel Long-Acting GLP-2, HM15912, for Short Bowel Syndrome
  • H2S Overproduction and Colonic Hypomotility in DM
Show more Gastrointestinal, Hepatic, Pulmonary, and Renal

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