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
  • 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
Pharmacological Reviews
  • 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
Pharmacological Reviews

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
  • Submit
  • Visit Pharm Rev on Facebook
  • Follow Pharm Rev on Twitter
  • Follow ASPET on LinkedIn
Review ArticleReview Article

Activation and Regulation of Purinergic P2X Receptor Channels

Claudio Coddou, Zonghe Yan, Tomas Obsil, J. Pablo Huidobro-Toro and Stanko S. Stojilkovic
David R. Sibley, ASSOCIATE EDITOR
Pharmacological Reviews September 2011, 63 (3) 641-683; DOI: https://doi.org/10.1124/pr.110.003129
Claudio Coddou
Section on Cellular Signaling, Program in Developmental Neuroscience, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (C.C., Z.Y., S.S.S.); Department of Physical and Macromolecular Chemistry, Faculty of Science, Charles University, Prague, Czech Republic (T.O.); and Centro de Envejecimiento y Regeneración, Centro Regulación Celular y Patología Prof. J.V. Luco, Instituto Milenio de Biología Fundamental y Aplicada, Departamento de Fisiología, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago, Chile (J.P.H.-T.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zonghe Yan
Section on Cellular Signaling, Program in Developmental Neuroscience, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (C.C., Z.Y., S.S.S.); Department of Physical and Macromolecular Chemistry, Faculty of Science, Charles University, Prague, Czech Republic (T.O.); and Centro de Envejecimiento y Regeneración, Centro Regulación Celular y Patología Prof. J.V. Luco, Instituto Milenio de Biología Fundamental y Aplicada, Departamento de Fisiología, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago, Chile (J.P.H.-T.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tomas Obsil
Section on Cellular Signaling, Program in Developmental Neuroscience, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (C.C., Z.Y., S.S.S.); Department of Physical and Macromolecular Chemistry, Faculty of Science, Charles University, Prague, Czech Republic (T.O.); and Centro de Envejecimiento y Regeneración, Centro Regulación Celular y Patología Prof. J.V. Luco, Instituto Milenio de Biología Fundamental y Aplicada, Departamento de Fisiología, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago, Chile (J.P.H.-T.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J. Pablo Huidobro-Toro
Section on Cellular Signaling, Program in Developmental Neuroscience, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (C.C., Z.Y., S.S.S.); Department of Physical and Macromolecular Chemistry, Faculty of Science, Charles University, Prague, Czech Republic (T.O.); and Centro de Envejecimiento y Regeneración, Centro Regulación Celular y Patología Prof. J.V. Luco, Instituto Milenio de Biología Fundamental y Aplicada, Departamento de Fisiología, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago, Chile (J.P.H.-T.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stanko S. Stojilkovic
Section on Cellular Signaling, Program in Developmental Neuroscience, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (C.C., Z.Y., S.S.S.); Department of Physical and Macromolecular Chemistry, Faculty of Science, Charles University, Prague, Czech Republic (T.O.); and Centro de Envejecimiento y Regeneración, Centro Regulación Celular y Patología Prof. J.V. Luco, Instituto Milenio de Biología Fundamental y Aplicada, Departamento de Fisiología, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago, Chile (J.P.H.-T.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David R. Sibley
Section on Cellular Signaling, Program in Developmental Neuroscience, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (C.C., Z.Y., S.S.S.); Department of Physical and Macromolecular Chemistry, Faculty of Science, Charles University, Prague, Czech Republic (T.O.); and Centro de Envejecimiento y Regeneración, Centro Regulación Celular y Patología Prof. J.V. Luco, Instituto Milenio de Biología Fundamental y Aplicada, Departamento de Fisiología, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago, Chile (J.P.H.-T.)
Roles: ASSOCIATE EDITOR
  • 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

Mammalian ATP-gated nonselective cation channels (P2XRs) can be composed of seven possible subunits, denoted P2X1 to P2X7. Each subunit contains a large ectodomain, two transmembrane domains, and intracellular N and C termini. Functional P2XRs are organized as homomeric and heteromeric trimers. This review focuses on the binding sites involved in the activation (orthosteric) and regulation (allosteric) of P2XRs. The ectodomains contain three ATP binding sites, presumably located between neighboring subunits and formed by highly conserved residues. The detection and coordination of three ATP phosphate residues by positively charged amino acids are likely to play a dominant role in determining agonist potency, whereas an AsnPheArg motif may contribute to binding by coordinating the adenine ring. Nonconserved ectodomain histidines provide the binding sites for trace metals, divalent cations, and protons. The transmembrane domains account not only for the formation of the channel pore but also for the binding of ivermectin (a specific P2X4R allosteric regulator) and alcohols. The N- and C- domains provide the structures that determine the kinetics of receptor desensitization and/or pore dilation and are critical for the regulation of receptor functions by intracellular messengers, kinases, reactive oxygen species and mercury. The recent publication of the crystal structure of the zebrafish P2X4.1R in a closed state provides a major advance in the understanding of this family of receptor channels. We will discuss data obtained from numerous site-directed mutagenesis experiments accumulated during the last 15 years with reference to the crystal structure, allowing a structural interpretation of the molecular basis of orthosteric and allosteric ligand actions.

Footnotes

  • This article is available online at http://pharmrev.aspetjournals.org.

    doi:10.1124/pr.110.003129.

  • U.S. Government work not protected by U.S. copyright
View Full Text

PharmRev 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

Pharmacological Reviews: 63 (3)
Pharmacological Reviews
Vol. 63, Issue 3
1 Sep 2011
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • 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 Pharmacological Reviews 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.
Activation and Regulation of Purinergic P2X Receptor Channels
(Your Name) has forwarded a page to you from Pharmacological Reviews
(Your Name) thought you would be interested in this article in Pharmacological Reviews.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Review ArticleReview Article

Activation and Regulation of Purinergic P2X Receptor Channels

Claudio Coddou, Zonghe Yan, Tomas Obsil, J. Pablo Huidobro-Toro and Stanko S. Stojilkovic
Pharmacological Reviews September 1, 2011, 63 (3) 641-683; DOI: https://doi.org/10.1124/pr.110.003129

Citation Manager Formats

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

Share
Review ArticleReview Article

Activation and Regulation of Purinergic P2X Receptor Channels

Claudio Coddou, Zonghe Yan, Tomas Obsil, J. Pablo Huidobro-Toro and Stanko S. Stojilkovic
Pharmacological Reviews September 1, 2011, 63 (3) 641-683; DOI: https://doi.org/10.1124/pr.110.003129
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
    • I. Introduction
    • II. Molecular and Crystal Structure of P2X2 Receptors
    • III. Orthosteric Binding Sites and Receptor Function
    • IV. Allosteric Binding Sites and Receptor Function
    • V. Future Directions
    • VI. Conclusions
    • Acknowledgments
    • Authorship Contributions
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • The Quest to Define and Target Cellular Senescence
  • Nanozymes for viral diagnosis and therapy
  • Structure and Inhibition of NLRP3 Inflammasome
Show more Review Articles

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Pharmacological Reviews
  • 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
  • Molecular Pharmacology
  • Pharmacology Research & Perspectives
ISSN 1521-0081 (Online)

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