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
Drug Metabolism & Disposition
  • 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
Drug Metabolism & Disposition

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 dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

Identification of Multiple Binding Sites for Substrate Transport in Bovine Organic Anion Transporting Polypeptide 1a2

Xiaoxiao Liu, Jiujiu Huang, Yongxue Sun, Kai Zhan, Zheren Zhang and Mei Hong
Drug Metabolism and Disposition March 2013, 41 (3) 602-607; DOI: https://doi.org/10.1124/dmd.112.047910
Xiaoxiao Liu
College of Life Science and Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms (X.L., J.H., K.Z., M.H.), and College of Veterinary Medicine (Y.S., Z.Z.), South China Agricultural University, Guangzhou, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jiujiu Huang
College of Life Science and Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms (X.L., J.H., K.Z., M.H.), and College of Veterinary Medicine (Y.S., Z.Z.), South China Agricultural University, Guangzhou, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yongxue Sun
College of Life Science and Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms (X.L., J.H., K.Z., M.H.), and College of Veterinary Medicine (Y.S., Z.Z.), South China Agricultural University, Guangzhou, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kai Zhan
College of Life Science and Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms (X.L., J.H., K.Z., M.H.), and College of Veterinary Medicine (Y.S., Z.Z.), South China Agricultural University, Guangzhou, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zheren Zhang
College of Life Science and Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms (X.L., J.H., K.Z., M.H.), and College of Veterinary Medicine (Y.S., Z.Z.), South China Agricultural University, Guangzhou, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mei Hong
College of Life Science and Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms (X.L., J.H., K.Z., M.H.), and College of Veterinary Medicine (Y.S., Z.Z.), South China Agricultural University, Guangzhou, China
  • 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

Organic anion transporting polypeptides (OATP) have been extensively recognized as key determinants of absorption, distribution, metabolism, and excretion of various drugs because of their broad substrate specificity, wide tissue distribution, and the involvement of drug-drug interaction. As the first cloned human OATP, OATP1A2 has been found to transport a wide spectrum of endogenous and exogenous compounds. Bovine Oapt1a2 shared high homology with the human transporter and is considered as its functional ortholog. In the present study, we expressed bovine Oatp1a2 in human embryonic kidney 293 cells and found that, unlike human OATP1A2, the transport of estrone-3-sulfate (E-3-S) exhibited biphasic saturation kinetics. The Km values are 0.25 ± 0.08 and 46.6 ± 18.5 µM, and Vmax values were 24.5 ±4.4 and 375 ± 142 pmol/mg protein/min for high- and low-affinity sites, respectively, suggesting the presence of multiple binding sites. Further study on other Oatp1a2 substrates showed that the high affinity component for E-3-S is responsible for the interaction with taurocholate, bromsulphthalein, and rifampicin and is sensitive to proton concentration change, whereas the low affinity binding site is only involved in the binding of the antitumor drug methotrexate and had no response to change of pH.

Footnotes

  • This work was supported by the High-Level Returned Overseas Talents–funded grant; and Guangdong Province Talent Introduction Project Grant (to M.H.).

  • dx.doi.org/10.1124/dmd.112.047910.

  • Received August 14, 2012.
  • Accepted December 19, 2012.
  • Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
View Full Text

 

DMD 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

Drug Metabolism and Disposition: 41 (3)
Drug Metabolism and Disposition
Vol. 41, Issue 3
1 Mar 2013
  • 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 Drug Metabolism & Disposition 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.
Identification of Multiple Binding Sites for Substrate Transport in Bovine Organic Anion Transporting Polypeptide 1a2
(Your Name) has forwarded a page to you from Drug Metabolism & Disposition
(Your Name) thought you would be interested in this article in Drug Metabolism & Disposition.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Bovine Oatp1a2 Contains Multiple Substrate Binding Sites

Xiaoxiao Liu, Jiujiu Huang, Yongxue Sun, Kai Zhan, Zheren Zhang and Mei Hong
Drug Metabolism and Disposition March 1, 2013, 41 (3) 602-607; DOI: https://doi.org/10.1124/dmd.112.047910

Citation Manager Formats

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

Share
Research ArticleArticle

Bovine Oatp1a2 Contains Multiple Substrate Binding Sites

Xiaoxiao Liu, Jiujiu Huang, Yongxue Sun, Kai Zhan, Zheren Zhang and Mei Hong
Drug Metabolism and Disposition March 1, 2013, 41 (3) 602-607; DOI: https://doi.org/10.1124/dmd.112.047910
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
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Determination of Acyl-, O-, and N-Glucuronide
  • TMDD Affects PK of IL-10 Fc-fusion Proteins
  • Uptake as the RDS in Pevonedistat Hepatic Clearance
Show more Articles

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 DMD
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Journal of Pharmacology and Experimental Therapeutics
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-009X (Online)

Copyright © 2022 by the American Society for Pharmacology and Experimental Therapeutics