Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • 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
  • 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
    • 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
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

P-Glycoprotein Substrates and Antagonists Cluster into Two Distinct Groups

Stefania Scala, Nadia Akhmed, U. S. Rao, Ken Paull, Lu-Bin Lan, Bruce Dickstein, Jong-Seok Lee, Galal H. Elgemeie, Wilfred D. Stein and Susan E. Bates
Molecular Pharmacology June 1997, 51 (6) 1024-1033; DOI: https://doi.org/10.1124/mol.51.6.1024
Stefania Scala
1 2 3 4 5 6
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nadia Akhmed
1 2 3 4 5 6
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
U. S. Rao
1 2 3 4 5 6
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ken Paull
1 2 3 4 5 6
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lu-Bin Lan
1 2 3 4 5 6
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bruce Dickstein
1 2 3 4 5 6
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jong-Seok Lee
1 2 3 4 5 6
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Galal H. Elgemeie
1 2 3 4 5 6
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wilfred D. Stein
1 2 3 4 5 6
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Susan E. Bates
1 2 3 4 5 6
  • 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

To gather further insight into the interaction between P-glycoprotein (Pgp) and its substrates, 167 compounds were analyzed in multidrug resistant human colon carcinoma cells. These compounds were selected from the National Cancer Institute Drug Screen repository using computer-generated correlations with known Pgp substrates and antagonists. The compounds were prospectively defined as Pgp substrates if cytotoxicity was increased ≥4-fold by the addition of cyclosporin A (CsA) and as Pgp antagonists if inhibition of efflux increased rhodamine accumulation by 4-fold. Among the 84 agents that met either criterion, 35 met only the criterion for substrates, 42 met only the criterion for antagonists, and only seven met both criteria. Thus, compounds interacting with Pgp form two distinct groups: one comprising cytotoxic compounds that are transported and have poor or no antagonistic activity and a second comprising compounds with antagonistic activity and no evidence of significant transport. Vinblastine accumulation and kinetic studies performed on a subset of 18 compounds similarly differentiated substrates and antagonists, but inhibition of 3H-azidopine labeling and induction of ATPase activity did not. These data support an emerging concept of Pgp in which multiple regions instead of specific sites are involved in drug transport.

Footnotes

    • Received June 20, 1996.
    • Accepted February 25, 1997.
  • Send reprint requests to: Susan E. Bates, M.D., Bldg. 10/Rm. 12N226, NCI/NIH, 9000 Rockville Pike, Bethesda, MD 20892. E-mail: sebates{at}helix.nih.gov

  • 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: 51 (6)
Molecular Pharmacology
Vol. 51, Issue 6
1 Jun 1997
  • 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.
P-Glycoprotein Substrates and Antagonists Cluster into Two Distinct Groups
(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

P-Glycoprotein Substrates and Antagonists Cluster into Two Distinct Groups

Stefania Scala, Nadia Akhmed, U. S. Rao, Ken Paull, Lu-Bin Lan, Bruce Dickstein, Jong-Seok Lee, Galal H. Elgemeie, Wilfred D. Stein and Susan E. Bates
Molecular Pharmacology June 1, 1997, 51 (6) 1024-1033; DOI: https://doi.org/10.1124/mol.51.6.1024

Citation Manager Formats

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

P-Glycoprotein Substrates and Antagonists Cluster into Two Distinct Groups

Stefania Scala, Nadia Akhmed, U. S. Rao, Ken Paull, Lu-Bin Lan, Bruce Dickstein, Jong-Seok Lee, Galal H. Elgemeie, Wilfred D. Stein and Susan E. Bates
Molecular Pharmacology June 1, 1997, 51 (6) 1024-1033; DOI: https://doi.org/10.1124/mol.51.6.1024
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Experimental Procedures
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Positive Allosteric Modulation of the mGlu5 Receptor
  • 6-Methylflavone Blocks Bitterness of Tenofovir
  • Correction of mutant CNGA3 channel trafficking defect
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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics