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
Molecular Pharmacology
  • 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
Molecular Pharmacology

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 molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

ATP, an Agonist at the Rat P2Y4 Receptor, Is an Antagonist at the Human P2Y4 Receptor

Charles Kennedy, Ai-Dong Qi, Christopher L. Herold, T. Kendall Harden and Robert A. Nicholas
Molecular Pharmacology May 2000, 57 (5) 926-931;
Charles Kennedy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ai-Dong Qi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christopher L. Herold
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
T. Kendall Harden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robert A. Nicholas
  • 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 nucleotide selectivities of the human P2Y4(hP2Y4) and rat P2Y4 (rP2Y4) receptor stably expressed in 1321N1 human astrocytoma cells were determined by measuring increases in intracellular [Ca2+] under conditions that minimized metabolism, bioconversion, and endogenous nucleotide release. In cells expressing the hP2Y4 receptor, UTP, GTP, and ITP all increased intracellular [Ca2+] with a rank order of potency of UTP (0.55) > GTP (6.59) = ITP (7.38), (EC50, μM). ATP, CTP, xanthine 5′-triphosphate (XTP), and diadenosine 5′,5‴-P1,P4-tetraphosphate (Ap4A), all at 100 μM, were inactive at the hP2Y4 receptor. In cells expressing the rP2Y4receptor, all seven nucleotides increased intracellular [Ca2+] with similar maximal effects and a rank order of potency of UTP (0.20) > ATP (0.51) > Ap4A (1.24) ≈ ITP (1.82) ≈ GTP (2.28) > CTP (7.24) > XTP (22.9). Because ATP is inactive at the hP2Y4 receptor, we assessed whether ATP displayed antagonist activity. When coapplied, ATP shifted the concentration-response curve to UTP rightward in a concentration-dependent manner, with no change in the maximal response. A Schild plot derived from these data gave a pA2 value of 6.15 (KB = 708 nM) and a slope near unity. Additionally, CTP and Ap4A (each at 100 μM) inhibited the response to an EC50 concentration of UTP by ∼40 and ∼50%, respectively, whereas XTP had no effect. The inhibitory effects of ATP, CTP, and Ap4A were reversible on washout. Thus, ATP is a potent agonist at the rP2Y4receptor but is a competitive antagonist with moderate potency at the hP2Y4 receptor.

Footnotes

  • Send reprint requests to: Dr. Robert Nicholas, Department of Pharmacology, University of North Carolina, CB #7365 Mary Ellen Jones Bldg., Chapel Hill, NC 27599-7365. E-mail:nicholas{at}med.unc.edu

  • This work was supported by United States Public Health Service Grant GM38213 (T.K.H., R.A.N.) and grants from The Wellcome Trust and The Caledonian Research Foundation (C.K.). During this study, R.A.N. was an Established Investigator of the American Heart Association.

  • Abbreviations:
    hP2Y4
    human P2Y4receptor
    Ap4A
    diadenosine 5′, 5‴-P1,P4-tetraphosphate
    rP2Y4
    rat P2Y4 receptor
    XTP
    xanthine 5′-triphosphate
    NDPK
    nucleoside diphosphokinase
    • Received September 20, 1999.
    • Accepted January 18, 2000.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

MolPharm 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

Molecular Pharmacology: 57 (5)
Molecular Pharmacology
Vol. 57, Issue 5
1 May 2000
  • 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 Molecular Pharmacology 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.
ATP, an Agonist at the Rat P2Y4 Receptor, Is an Antagonist at the Human P2Y4 Receptor
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

ATP, an Agonist at the Rat P2Y4 Receptor, Is an Antagonist at the Human P2Y4 Receptor

Charles Kennedy, Ai-Dong Qi, Christopher L. Herold, T. Kendall Harden and Robert A. Nicholas
Molecular Pharmacology May 1, 2000, 57 (5) 926-931;

Citation Manager Formats

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

Share
Research ArticleArticle

ATP, an Agonist at the Rat P2Y4 Receptor, Is an Antagonist at the Human P2Y4 Receptor

Charles Kennedy, Ai-Dong Qi, Christopher L. Herold, T. Kendall Harden and Robert A. Nicholas
Molecular Pharmacology May 1, 2000, 57 (5) 926-931;
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Experimental Procedures
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Mechanism of the selective action of paraherquamide A
  • Fatty Acid Amide Hydrolase in Cisplatin Nephrotoxicity
  • Use-Dependent Relief of A-887826 Inhibition
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 Molecular Pharmacology
  • 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
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics