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

In Vitro Investigation of Amyloid-β Hepatobiliary Disposition in Sandwich-Cultured Primary Rat Hepatocytes

Loqman A. Mohamed and Amal Kaddoumi
Drug Metabolism and Disposition October 2013, 41 (10) 1787-1796; DOI: https://doi.org/10.1124/dmd.113.052514
Loqman A. Mohamed
Department of Basic Pharmaceutical Science, College of Pharmacy, University of Louisiana at Monroe, Monroe, Louisiana
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Amal Kaddoumi
Department of Basic Pharmaceutical Science, College of Pharmacy, University of Louisiana at Monroe, Monroe, Louisiana
  • 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

Failure in amyloid-β (Aβ) systemic clearance across the liver has been suggested to play a role in Aβ brain accumulation and thus to contribute largely to the pathology of Alzheimer’s disease (AD). The purpose of this study was to characterize in vitro the transport mechanisms of Aβ40 across the liver using sandwich-cultured primary rat hepatocytes (SCHs) and to determine its biliary clearance (CLbile) and biliary excretion index (BEI%). 125I-Aβ40 BEI% was time dependent and reached steady state at 30 minutes, with an average value of 29.8% and a CLbile of 1.47 ml/min per kilogram of body weight. The role of low-density lipoprotein receptor–related protein-1 (LRP1) in mediating the basolateral uptake of 125I-Aβ40 in SCHs was assessed using receptor-associated protein (RAP, 2 µM). A significant reduction in 125I-Aβ40 BEI% and CLbile with RAP was observed, demonstrating a major contribution of LRP1 in mediating hepatic uptake of intact 125I-Aβ40 via transcytosis. Furthermore, activity studies suggested a lower role of receptor for advanced glycation end products (RAGE) in 125I-Aβ40 hepatic uptake. Verapamil (50 µM) and valspodar (20 µM) significantly reduced 125I-Aβ40 BEI%, indicating a role for P-glycoprotein (P-gp) in the biliary excretion of 125I-Aβ40 in SCHs. LRP1- and P-gp-mediated 125I-Aβ40 biliary excretion was inducible and increased BEI% by 26% after rifampicin pretreatment. In conclusion, our findings demonstrated that besides LRP1, P-gp and, to a lesser extent, RAGE are involved in 125I-Aβ40 hepatobiliary disposition and support the use of enhancement of Aβ hepatic clearance via LRP1 and P-gp induction as a novel therapeutic approach for the prevention and treatment of AD.

Footnotes

    • Received April 18, 2013.
    • Accepted July 12, 2013.
  • This work was supported by a fellowship from the Ministry of Higher Education of the Libyan government; and the Libyan North American Scholarship Program (to L.A.M.).

  • dx.doi.org/10.1124/dmd.113.052514.

  • 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 (10)
Drug Metabolism and Disposition
Vol. 41, Issue 10
1 Oct 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.
In Vitro Investigation of Amyloid-β Hepatobiliary Disposition in Sandwich-Cultured Primary Rat Hepatocytes
(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

Aβ40 Biliary Excretion in SCHs

Loqman A. Mohamed and Amal Kaddoumi
Drug Metabolism and Disposition October 1, 2013, 41 (10) 1787-1796; DOI: https://doi.org/10.1124/dmd.113.052514

Citation Manager Formats

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

Share
Research ArticleArticle

Aβ40 Biliary Excretion in SCHs

Loqman A. Mohamed and Amal Kaddoumi
Drug Metabolism and Disposition October 1, 2013, 41 (10) 1787-1796; DOI: https://doi.org/10.1124/dmd.113.052514
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
    • 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