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
Rapid CommunicationShort Communication

Effect of Glucagon-Like Peptide 2 on Hepatic, Renal, and Intestinal Disposition of 1-Chloro-2,4-dinitrobenzene

Silvina S. M. Villanueva, Virginia G. Perdomo, María L. Ruiz, Juan P. Rigalli, Agostina Arias, Marcelo G. Luquita, Mary Vore, Viviana A. Catania and Aldo D. Mottino
Drug Metabolism and Disposition July 2012, 40 (7) 1252-1258; DOI: https://doi.org/10.1124/dmd.111.044339
Silvina S. M. Villanueva
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Virginia G. Perdomo
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
María L. Ruiz
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Juan P. Rigalli
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Agostina Arias
  • 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
Mary Vore
  • 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
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 ability of the liver, small intestine, and kidney to synthesize and subsequently eliminate dinitrophenyl-S-glutathione (DNP-SG), a substrate for multidrug resistance-associated protein 2 (Mrp2), was assessed in rats treated with glucagon-like peptide 2 (GLP-2, 12 μg/100 g b.wt. s.c. every 12 h for 5 consecutive days). An in vivo perfused jejunum model with simultaneous bile and urine collection was used. A single intravenous dose of 30 μmol/kg b.wt. 1-chloro-2,4-dinitrobenzene (CDNB) was administered, and its conjugate, DNP-SG, and dinitrophenyl cysteinyl glycine (DNP-CG), resulting from the action of γ-glutamyltransferase on DNP-SG, were determined in bile, intestinal perfusate, and urine by high-performance liquid chromatography. Tissue content of DNP-SG was also assessed in liver, intestine, and kidneys. Biliary excretion of DNP-SG+DNP-CG was decreased in GLP-2 rats with respect to controls. In contrast, their intestinal excretion was substantially increased, whereas urinary elimination was not affected. Western blot and real-time polymerase chain reaction studies revealed preserved levels of Mrp2 protein and mRNA in liver and renal cortex and a significant increase in intestine in response to GLP-2 treatment. Tissue content of DNP-SG detected 5 min after CDNB administration was decreased in liver, increased in intestine, and unchanged in kidney in GLP-2 versus control group, consistent with GLP-2-induced down-regulation of expression of glutathione transferase (GST) Mu in liver and up-regulation of GST-Alpha in intestine at both protein and mRNA levels. In conclusion, GLP-2 induced selective changes in hepatic and intestinal disposition of a common GST and Mrp2 substrate administered systemically that could be of pharmacological or toxicological relevance under therapeutic treatment conditions.

Footnotes

  • This work was supported by the National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development [Grant R01-HD58299] (to M.V.); Agencia Nacional de Promoción Científica y Tecnológica [Grant PICT 2007-1637]; Consejo Nacional de Investigaciones Científicas y Técnicas [Grant PIP 112-200801-00691] (to A.D.M.); and Agencia Nacional de Promoción Científica y Tecnológica [Grant PICT 2010-1475] (to S.S.M.V.).

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

    http://dx.doi.org/10.1124/dmd.111.044339.

  • ABBREVIATIONS:

    GLP-2
    glucagon-like peptide 2
    GST
    glutathione transferase
    Mrp2
    multidrug resistance-associated protein 2
    IBD
    inflammatory bowel diseases
    GLP-2R
    glucagon-like peptide 2 receptor
    CDNB
    1-chloro-2,4-dinitrobenzene
    DNP-CG
    dinitrophenyl cysteinyl glycine
    DNP-SG
    dinitrophenyl-S-glutathione
    PBS
    phosphate-buffered saline.

  • Received December 16, 2011.
  • Accepted March 27, 2012.
  • Copyright © 2012 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: 40 (7)
Drug Metabolism and Disposition
Vol. 40, Issue 7
1 Jul 2012
  • 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.
Effect of Glucagon-Like Peptide 2 on Hepatic, Renal, and Intestinal Disposition of 1-Chloro-2,4-dinitrobenzene
(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
Rapid CommunicationShort Communication

EFFECT OF GLP-2 ON CDNB DISPOSITION

Silvina S. M. Villanueva, Virginia G. Perdomo, María L. Ruiz, Juan P. Rigalli, Agostina Arias, Marcelo G. Luquita, Mary Vore, Viviana A. Catania and Aldo D. Mottino
Drug Metabolism and Disposition July 1, 2012, 40 (7) 1252-1258; DOI: https://doi.org/10.1124/dmd.111.044339

Citation Manager Formats

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

Share
Rapid CommunicationShort Communication

EFFECT OF GLP-2 ON CDNB DISPOSITION

Silvina S. M. Villanueva, Virginia G. Perdomo, María L. Ruiz, Juan P. Rigalli, Agostina Arias, Marcelo G. Luquita, Mary Vore, Viviana A. Catania and Aldo D. Mottino
Drug Metabolism and Disposition July 1, 2012, 40 (7) 1252-1258; DOI: https://doi.org/10.1124/dmd.111.044339
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 and Discussion
    • Authorship Contributions
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Preincubation Effects on Inhibition of OCT1 by CsA
  • Carbamazepine Metabolite and Hypersensitivity Reactions
  • SULT4A1 Preserves Mitochondrial Function
Show more Short Communications

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 © 2023 by the American Society for Pharmacology and Experimental Therapeutics