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
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
    • 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 ArticleArticle

Role of Adenosine A1 Receptors in Modulating Extracellular Adenosine Levels

Bradley T. Andresen, Delbert G. Gillespie, Zaichuan Mi, Raghvendra K. Dubey and Edwin K. Jackson
Journal of Pharmacology and Experimental Therapeutics October 1999, 291 (1) 76-80;
Bradley T. Andresen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Delbert G. Gillespie
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zaichuan Mi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Raghvendra K. Dubey
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Edwin K. Jackson
  • 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 purpose of this investigation was to test the hypothesis that A1 receptors modulate extracellular levels of adenosine in cardiovascular tissues. Rat cardiac fibroblasts and human aortic vascular smooth muscle cells were cultured to confluence and various pharmacological agents were applied to the cultures. The extracellular fluid was extracted and adenosine concentrations were measured by HPLC. Three selective A1 receptor antagonists, namely 8-cyclopentyl-1,3-dipropylxanthine, xanthine amine congener, and N-0840, at a concentration of 10 nM significantly increased extracellular levels of adenosine in both rat cardiac fibroblasts and human aortic vascular smooth muscle cells. Further studies in rat cardiac fibroblasts revealed that the effects of A1receptor blockade on extracellular adenosine levels were concentration dependent and prevented by inhibition of Gi proteins with pertussis toxin or blockade of ecto-5′-nucleotidase with α,β-methyleneadenosine-5′-diphosphate. In cardiac fibroblasts in which the extracellular levels of endogenous adenosine were increased, the ability of A1 receptor blockade to augment extracellular adenosine was attenuated. A time-course study revealed a time lag of several hours between blockade of A1 receptors and increases in extracellular adenosine levels. These data suggest that A1 receptors function to detect the long-term levels of extracellular adenosine, and appropriately adjust extracellular adenosine levels by a slow-onset mechanism involving Giproteins and ecto-5′nucleotidase.

Footnotes

  • Send reprint requests to: Dr. Edwin K. Jackson, Center for Clinical Pharmacology, University of Pittsburgh Medical Center, 623 Scaife Hall, 200 Lothrop St., Pittsburgh, PA 15213-2582. E-mail:edj+{at}pitt.edu

  • ↵1 This work was supported by National Institutes of Health Grants HL55314 and HL35909.

  • Abbreviations:
    AMPCP
    α,β-methyleneadenosine-5′-diphosphate
    DPCPX
    8-cyclopentyl-1,3-dipropylxanthine
    XAC
    xanthine amine congener
    • Received March 25, 1999.
    • Accepted June 1, 1999.
  • 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: 291 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 291, Issue 1
1 Oct 1999
  • 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 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.
Role of Adenosine A1 Receptors in Modulating Extracellular Adenosine Levels
(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 ArticleArticle

Role of Adenosine A1 Receptors in Modulating Extracellular Adenosine Levels

Bradley T. Andresen, Delbert G. Gillespie, Zaichuan Mi, Raghvendra K. Dubey and Edwin K. Jackson
Journal of Pharmacology and Experimental Therapeutics October 1, 1999, 291 (1) 76-80;

Citation Manager Formats

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

Share
Research ArticleArticle

Role of Adenosine A1 Receptors in Modulating Extracellular Adenosine Levels

Bradley T. Andresen, Delbert G. Gillespie, Zaichuan Mi, Raghvendra K. Dubey and Edwin K. Jackson
Journal of Pharmacology and Experimental Therapeutics October 1, 1999, 291 (1) 76-80;
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
    • Materials and Methods
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • PST3093 Stimulates SERCA2a and Improves Cardiac Function
  • CRV431 Decreases Liver Fibrosis and Tumor Development
  • Meeting Report for the ASPET–Ray Fuller Symposium: Cellular Mechanisms and Novel Strategies for Pain Control
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 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