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
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
  • My Cart
Journal of Pharmacology and Experimental Therapeutics

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 jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleCardiovascular

Stimulation of G Protein–Coupled Bile Acid Receptor Enhances Vascular Endothelial Barrier Function via Activation of Protein Kinase A and Rac1

Taiki Kida, Keisuke Omori, Masatoshi Hori, Hiroshi Ozaki and Takahisa Murata
Journal of Pharmacology and Experimental Therapeutics January 2014, 348 (1) 125-130; DOI: https://doi.org/10.1124/jpet.113.209288
Taiki Kida
Department of Veterinary Pharmacology (T.K., K.O., M.H., H.O., T.M.) and Department of Animal Radiology (T.M.), Graduate School of Agriculture and Life Sciences, The University of Tokyo, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Keisuke Omori
Department of Veterinary Pharmacology (T.K., K.O., M.H., H.O., T.M.) and Department of Animal Radiology (T.M.), Graduate School of Agriculture and Life Sciences, The University of Tokyo, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Masatoshi Hori
Department of Veterinary Pharmacology (T.K., K.O., M.H., H.O., T.M.) and Department of Animal Radiology (T.M.), Graduate School of Agriculture and Life Sciences, The University of Tokyo, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hiroshi Ozaki
Department of Veterinary Pharmacology (T.K., K.O., M.H., H.O., T.M.) and Department of Animal Radiology (T.M.), Graduate School of Agriculture and Life Sciences, The University of Tokyo, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Takahisa Murata
Department of Veterinary Pharmacology (T.K., K.O., M.H., H.O., T.M.) and Department of Animal Radiology (T.M.), Graduate School of Agriculture and Life Sciences, The University of Tokyo, Japan
  • 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 + SI
  • PDF
Loading

Abstract

Bile acids are end products of cholesterol metabolism, and they constantly exist at high concentrations in the blood. Since vascular endothelial cells express G protein–coupled bile acid receptor (GPBAR), bile acids potentially modulate endothelial function. Here, we investigated whether and how GPBAR agonism affects endothelial barrier function. In bovine aortic endothelial cells (BAECs), treatment with a GPBAR agonist, taurolithocholic acid (TLCA) increased the transendothelial electrical resistance. In addition, TLCA suppressed the thrombin-induced dextran infiltration through the endothelial monolayer. Knockdown of GPBAR abolished the inhibitory effect of TLCA on hyperpermeability. These results indicate that stimulation of GPBAR enhances endothelial barrier function. TLCA increased intracellular cAMP production in BAECs. Inhibition of protein kinase A (PKA) or Rac1 significantly attenuated the TLCA-induced endothelial barrier protection. TLCA induced cortical actin polymerization, which was attenuated by a Rac1 inhibitor. In vivo, local administration of TLCA into the mouse ear significantly inhibited vascular leakage and edema formation induced by croton oil or vascular endothelial growth factor. These results indicate that stimulation of GPBAR enhances endothelial barrier function by cAMP/PKA/Rac1-dependent cytoskeletal rearrangement.

Footnotes

    • Received August 31, 2013.
    • Accepted October 21, 2013.
  • This work was supported by the Japan Society for the Promotion of Science, The Naito Foundation, The Takeda Science Foundation, the Program for Promotion of Basic and Applied Researches for Innovations in Bio-oriented Industry, and the Japan Diabetes Foundation.

  • dx.doi.org/10.1124/jpet.113.209288.

  • ↵Embedded ImageThis article has supplemental material available at jpet.aspetjournals.org.

  • Copyright © 2013 by 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.
PreviousNext
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 348 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 348, Issue 1
1 Jan 2014
  • 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.
Stimulation of G Protein–Coupled Bile Acid Receptor Enhances Vascular Endothelial Barrier Function via Activation of Protein Kinase A and Rac1
(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 ArticleCardiovascular

GPBAR Enhances Endothelial Barrier Function

Taiki Kida, Keisuke Omori, Masatoshi Hori, Hiroshi Ozaki and Takahisa Murata
Journal of Pharmacology and Experimental Therapeutics January 1, 2014, 348 (1) 125-130; DOI: https://doi.org/10.1124/jpet.113.209288

Citation Manager Formats

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

GPBAR Enhances Endothelial Barrier Function

Taiki Kida, Keisuke Omori, Masatoshi Hori, Hiroshi Ozaki and Takahisa Murata
Journal of Pharmacology and Experimental Therapeutics January 1, 2014, 348 (1) 125-130; DOI: https://doi.org/10.1124/jpet.113.209288
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
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Improved Assessment of Cardiovascular Safety Data
  • β3-Agonist Improves Myocardial Stiffness
  • A Novel Inhibitor of Myocardial mPTP
Show more Cardiovascular

Similar Articles

  • 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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics