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
  • Log out
  • 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
  • Log out
  • 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

Induction of Rat Intestinal P-glycoprotein by Spironolactone and Its Effect on Absorption of Orally Administered Digoxin

Carolina I. Ghanem, Paula C. Gómez, María C. Arana, María Perassolo, Griselda Delli Carpini, Marcelo G. Luquita, Luis M. Veggi, Viviana A. Catania, Laura A. Bengochea and Aldo D. Mottino
Journal of Pharmacology and Experimental Therapeutics September 2006, 318 (3) 1146-1152; DOI: https://doi.org/10.1124/jpet.106.105668
Carolina I. Ghanem
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Paula C. Gómez
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
María C. Arana
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
María Perassolo
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Griselda Delli Carpini
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marcelo G. Luquita
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Luis M. Veggi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Viviana A. Catania
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Laura A. Bengochea
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Aldo D. Mottino
  • 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 effect of the diuretic spironolactone (SL) on expression and function of intestinal P-glycoprotein (P-gp), as well as its impact on intestinal absorption of digoxin, was explored. Rats were treated with daily doses of 200 μmol/kg b.wt. of SL intraperitoneally for 3 consecutive days. The small intestine was divided into four equal segments of ∼25 cm, with segment I being the most proximal. Brush-border membranes were isolated and used in analysis of P-gp expression by Western blot analysis. P-gp content increased in the SL group by 526, 292, 210, and 622% over controls for segments I, II, III, and IV, respectively. Up-regulation of apical P-gp was confirmed by immunofluorescence microscopy. P-gp transport activity was explored in intestinal sacs prepared from segment IV using two different model substrates. Serosal to mucosal transport (efflux) of rhodamine 123 was 140% higher, and mucosal to serosal transport (absorption) of digoxin was 40% lower in the SL group, both indicating increased P-gp function. In vivo experiments showed that intestinal absorption of a single dose of digoxin administered p.o. was attenuated by SL pretreatment. Thus, concentration of digoxin in portal and peripheral blood was lower in SL versus control groups, as well as its accumulation in kidney and liver. Urinary excretion of digoxin was significantly decreased in the SL group, probably reflecting decreased systemic availability of digoxin for subsequent urinary elimination. We conclude that SL induces P-gp expression with potential impact on intestinal absorption of substrates with therapeutic application.

Footnotes

  • This work was supported by grants from Universidad de Buenos Aires (B045), Consejo Nacional de Investigaciones Científicas y Técnicas (PIP 6442), and Agencia Nacional de Promoción Cientifica y Tecnológica (PICT 05-08418).

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

  • doi:10.1124/jpet.106.105668.

  • ABBREVIATIONS: P-gp, P-glycoprotein; SL, spironolactone; BBM, brush-border membrane; i.p., intraperitoneal.

    • Received April 3, 2006.
    • Accepted May 31, 2006.
  • 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 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 385, Issue 3
1 Jun 2023
  • 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 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.
Induction of Rat Intestinal P-glycoprotein by Spironolactone and Its Effect on Absorption of Orally Administered Digoxin
(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

Induction of Rat Intestinal P-glycoprotein by Spironolactone and Its Effect on Absorption of Orally Administered Digoxin

Carolina I. Ghanem, Paula C. Gómez, María C. Arana, María Perassolo, Griselda Delli Carpini, Marcelo G. Luquita, Luis M. Veggi, Viviana A. Catania, Laura A. Bengochea and Aldo D. Mottino
Journal of Pharmacology and Experimental Therapeutics September 1, 2006, 318 (3) 1146-1152; DOI: https://doi.org/10.1124/jpet.106.105668

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

Induction of Rat Intestinal P-glycoprotein by Spironolactone and Its Effect on Absorption of Orally Administered Digoxin

Carolina I. Ghanem, Paula C. Gómez, María C. Arana, María Perassolo, Griselda Delli Carpini, Marcelo G. Luquita, Luis M. Veggi, Viviana A. Catania, Laura A. Bengochea and Aldo D. Mottino
Journal of Pharmacology and Experimental Therapeutics September 1, 2006, 318 (3) 1146-1152; DOI: https://doi.org/10.1124/jpet.106.105668
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
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • BI 685509 Reduces Portal Hypertension in TAA Cirrhosis Model
  • CGRP signaling in visceral organ cross sensitization
  • 20-HETE Synthesis Inhibitor Suppresses Renal Fibrosis
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