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 ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

KF24345, an Adenosine Uptake Inhibitor, Suppresses Lipopolysaccharide-Induced Tumor Necrosis Factor-α Production and Leukopenia via Endogenous Adenosine in Mice

Tohru Noji, Makoto Takayama, Mirai Mizutani, Yuko Okamura, Haruki Takai, Akira Karasawa and Hideaki Kusaka
Journal of Pharmacology and Experimental Therapeutics January 2002, 300 (1) 200-205; DOI: https://doi.org/10.1124/jpet.300.1.200
Tohru Noji
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Makoto Takayama
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mirai Mizutani
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yuko Okamura
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Haruki Takai
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Akira Karasawa
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hideaki Kusaka
  • 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

3-[1-(6,7-Diethoxy-2-morpholinoquinazolin-4-yl)piperidin-4-yl]-1,6-dimethyl-2,4(1H,3H)-quinazolinedione hydrochloride (KF24345) is a novel potent adenosine uptake inhibitor. KF24345 inhibited [3H]adenosine uptake into erythrocytes from human, mouse, rabbit, and hamster with IC50 values of 59.5, 130.1, 104.2, and 30.9 nM, respectively. In mice, oral administration of KF24345 at 10 mg/kg almost completely inhibited the [3H]adenosine uptake into sampled blood cells at least up to 10 h of the administration. In this study, to examine whether the adenosine uptake inhibition exhibits anti-inflammatory effects, we determined the effects of KF24345 on lipopolysaccharide (LPS)-induced tumor necrosis factor-α (TNF-α) production and leukopenia in mice. KF24345 (10 mg/kg p.o.) significantly suppressed the elevation of serum TNF-α concentration after the LPS injection, and the suppressing effect of KF24345 was abolished by the treatment with 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol, a selective adenosine A2 receptor antagonist, but not with 8-(noradamantan-3-yl)-1,3-dipropylxanthine, a selective adenosine A1 receptor antagonist. KF24345 (10 mg/kg p.o.) also inhibited the decrease of leukocytes after the LPS injection, and 8-(p-sulfophenyl)theophylline, a nonselective adenosine receptor antagonist, completely reversed the inhibitory effect of KF24345. These results demonstrate that KF24345 inhibits LPS-induced TNF-α production and leukopenia via enhancing the effect of endogenous adenosine. It is thus suggested that the adenosine uptake inhibitor has anti-inflammatory effects in vivo and represents a novel therapeutic approach to the treatment of various inflammatory diseases.

  • Abbreviations

    KF24345
    3-[1-(6,7-diethoxy-2-morpholinoquinazolin-4-yl)piperidin-4-yl]-1,6-dimethyl-2,4(1H,3H)-quinazolinedione hydrochloride
    LPS
    lipopolysaccharide
    TNF-α
    tumor necrosis factor-α
    ZM 241385
    4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol
    8-SPT
    8-(p-sulfophenyl)theophylline
    R75231
    2-(aminocarbonyl)-N-(4-amino-2,6-dichlorophenyl)-4-[5,5-bis(4-fluorophenyl)pentyl]-1-piperazineacetamide
    KW-3902
    8-(noradamantan-3-yl)-1,3-dipropylxanthine
    • Received May 30, 2001.
    • Accepted September 21, 2001.
    • 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: 300 (1)
    Journal of Pharmacology and Experimental Therapeutics
    Vol. 300, Issue 1
    1 Jan 2002
    • 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.
    KF24345, an Adenosine Uptake Inhibitor, Suppresses Lipopolysaccharide-Induced Tumor Necrosis Factor-α Production and Leukopenia via Endogenous Adenosine in Mice
    (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 ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

    KF24345, an Adenosine Uptake Inhibitor, Suppresses Lipopolysaccharide-Induced Tumor Necrosis Factor-α Production and Leukopenia via Endogenous Adenosine in Mice

    Tohru Noji, Makoto Takayama, Mirai Mizutani, Yuko Okamura, Haruki Takai, Akira Karasawa and Hideaki Kusaka
    Journal of Pharmacology and Experimental Therapeutics January 1, 2002, 300 (1) 200-205; DOI: https://doi.org/10.1124/jpet.300.1.200

    Citation Manager Formats

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

    Share
    Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

    KF24345, an Adenosine Uptake Inhibitor, Suppresses Lipopolysaccharide-Induced Tumor Necrosis Factor-α Production and Leukopenia via Endogenous Adenosine in Mice

    Tohru Noji, Makoto Takayama, Mirai Mizutani, Yuko Okamura, Haruki Takai, Akira Karasawa and Hideaki Kusaka
    Journal of Pharmacology and Experimental Therapeutics January 1, 2002, 300 (1) 200-205; DOI: https://doi.org/10.1124/jpet.300.1.200
    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
      • Acknowledgments
      • Abbreviations
      • References
    • Figures & Data
    • Info & Metrics
    • eLetters
    • PDF

    Related Articles

    Cited By...

    More in this TOC Section

    • Lipopolysaccharide Induces Epithelium- and Prostaglandin E2-Dependent Relaxation of Mouse Isolated Trachea through Activation of Cyclooxygenase (COX)-1 and COX-2
    • Cannabinoid-Mediated Elevation of Intracellular Calcium: A Structure-Activity Relationship
    • Protease-Activated Receptor-2 Peptides Activate Neurokinin-1 Receptors in the Mouse Isolated Trachea
    Show more INFLAMMATION AND IMMUNOPHARMACOLOGY

    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 © 2022 by the American Society for Pharmacology and Experimental Therapeutics