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
Molecular Pharmacology
  • 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
Molecular Pharmacology

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

Competitive and Allosteric Interactions in Ligand Binding to P-glycoprotein as Observed on an Immobilized P-glycoprotein Liquid Chromatographic Stationary Phase

Lili Lu, Fabio Leonessa, Robert Clarke and Irving W. Wainer
Molecular Pharmacology January 2001, 59 (1) 62-68; DOI: https://doi.org/10.1124/mol.59.1.62
Lili Lu
Department of Pharmacology and the Lombardi Cancer Center, Georgetown University School of Medicine, Washington, DC
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Fabio Leonessa
Department of Pharmacology and the Lombardi Cancer Center, Georgetown University School of Medicine, Washington, DC
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robert Clarke
Department of Pharmacology and the Lombardi Cancer Center, Georgetown University School of Medicine, Washington, DC
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Irving W. Wainer
Department of Pharmacology and the Lombardi Cancer Center, Georgetown University School of Medicine, Washington, DC
  • 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

A liquid chromatographic stationary phase containing immobilized P-glycoprotein (Pgp) was synthesized using cell membranes obtained from Pgp-expressing cells. The resulting Pgp-stationary phase was used in frontal and zonal chromatographic studies to investigate the binding of vinblastine (VBL), doxorubicin (DOX), verapamil (VER), and cyclosporin A (CsA) to the immobilized Pgp. The compounds were added individually to the chromatographic system with or without ATP in the running buffer. Using this approach, dissociation constants were calculated for VBL (23.5 ± 7.8 nM), DOX (15.0 ± 3.2 μM), VER (54.2 ± 4.7 μM), and CsA [97.9 ± 19.4 nM (without ATP) and 62.5 ± 4.6 nM (with ATP)]. The compounds were also added in pairs using standard competitive chromatography procedures. The results of the study demonstrate that competitive interactions occurred between VBL and DOX, cooperative allosteric interactions occurred between VBL and CsA and ATP and CsA, and anticooperative allosteric interactions occurred between ATP and VBL and VER. The chromatographic studies indicate that the immobilized Pgp was modified by ligand and cofactor binding and that the stationary phase can be used to study drug-drug binding interactions on the Pgp molecule.

Footnotes

    • Received June 8, 2000.
    • Accepted September 29, 2000.
  • Send reprint requests to: Dr. Irving W. Wainer, Department of Pharmacology, Georgetown University School of Medicine, Rm. C305, Medical Dental Bldg., 3900 Reservoir Rd., NW, Washington, DC 20007. E-mail: waineri{at}gunet.georgetown.edu

  • This research was supported by National Institutes of Health Grant 2R42M56591-02 (I.W.W.).

  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

MolPharm 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

Molecular Pharmacology: 59 (1)
Molecular Pharmacology
Vol. 59, Issue 1
1 Jan 2001
  • 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 Molecular Pharmacology 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.
Competitive and Allosteric Interactions in Ligand Binding to P-glycoprotein as Observed on an Immobilized P-glycoprotein Liquid Chromatographic Stationary Phase
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Competitive and Allosteric Interactions in Ligand Binding to P-glycoprotein as Observed on an Immobilized P-glycoprotein Liquid Chromatographic Stationary Phase

Lili Lu, Fabio Leonessa, Robert Clarke and Irving W. Wainer
Molecular Pharmacology January 1, 2001, 59 (1) 62-68; DOI: https://doi.org/10.1124/mol.59.1.62

Citation Manager Formats

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

Share
Research ArticleArticle

Competitive and Allosteric Interactions in Ligand Binding to P-glycoprotein as Observed on an Immobilized P-glycoprotein Liquid Chromatographic Stationary Phase

Lili Lu, Fabio Leonessa, Robert Clarke and Irving W. Wainer
Molecular Pharmacology January 1, 2001, 59 (1) 62-68; DOI: https://doi.org/10.1124/mol.59.1.62
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
    • Acknowledgment
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Michaelis Menten quantification of GPCR-G protein signalling
  • Human mAb 3F1 targeting the fuctional epitopes of Siglec-15
  • The regulation and mechanisms of ImKTX58 on KV1.3 channel
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 Molecular Pharmacology
  • 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
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

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