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 ArticleCELLULAR AND MOLECULAR

Cross Talk between P2Y2 Nucleotide Receptors and CXC Chemokine Receptor 2 Resulting in Enhanced Ca2+ Signaling Involves Enhancement of Phospholipase C Activity and Is Enabled by Incremental Ca2+ Release in Human Embryonic Kidney Cells

Tim D. Werry, Graeme F. Wilkinson and Gary B. Willars
Journal of Pharmacology and Experimental Therapeutics November 2003, 307 (2) 661-669; DOI: https://doi.org/10.1124/jpet.103.055632
Tim D. Werry
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Graeme F. Wilkinson
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gary B. Willars
  • 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

We have shown previously that activation of endogenously expressed, Gαq/11-coupled P2Y2 nucleotide receptors with UTP reveals an intracellular Ca2+ response to activation of recombinant, Gαi-coupled CXC chemokine receptor 2 (CXCR2) in human embryonic kidney cells. Here, we characterize further this cross talk and demonstrate that phospholipase C (PLC) and inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]-dependent Ca2+ release underlies this potentiation. The putative Ins(1,4,5)P3 receptor antagonist 2-aminoethoxydiphenyl borane reduced the response to CXCR2 activation by interleukin-8, as did sustained inhibition of phosphatidylinositol 4-kinase with wortmannin, suggesting the involvement of phosphoinositides in the potentiation. Against a Li+ block of inositol monophosphatase activity, costimulation of P2Y2 nucleotide receptors and CXCR2 caused phosphoinositide accumulation that was significantly greater than that after activation of P2Y2 nucleotide receptors or CXCR2 alone, and was more than additive. Thus, PLC activity, as well as Ca2+ release, was enhanced. In these cells, agonist-mediated Ca2+ release was incremental in nature, suggesting that a potentiation of Ins(1,4,5)P3 generation in the presence of coactivation of P2Y2 nucleotide receptors and CXCR2 would be sufficient for additional Ca2+ release. Potentiated Ca2+ signaling by CXCR2 was markedly attenuated by expression of either regulator of G protein signaling 2 or the Gβγ-scavenger Gαt1 (transducin α subunit), indicating the involvement of Gαq and Gβγ subunits, respectively.

Footnotes

  • This work was jointly funded by the Biotechnology and Biological Sciences Research Council and AstraZeneca R&D Charnwood (Loughborough, UK).

  • DOI: 10.1124/jpet.103.055632.

  • ABBREVIATIONS: GPCR, G protein-coupled receptor; HEK, human embryonic kidney; HEK-CXCR2, human embryonic kidney cell with stable expression of recombinant human CXCR2; CXCR2, CXC chemokine receptor 2 or IL-8 receptor B; PTX, pertussis toxin; PLC, phospholipase C; Ins(1,4,5)P3, inositol 1,4,5-trisphosphate; AM, acetoxymethyl ester; IL-8, interleukin-8; 2-APB, 2-aminoethoxydiphenyl borane; RGS, regulator of G protein signaling; BSS, balanced salts solution; [Ca2+]i, intracellular Ca2+ concentration; GFP, green fluorescent protein; InsPx, inositol phosphates; PI 3-kinase, phosphatidylinositol 3-kinase; PI 4-kinase, phosphatidylinositol 4-kinase; PIP2, phosphatidylinositol 4,5-bisphosphate; PKC, protein kinase C; DMSO, dimethyl sulfoxide; PP, protein phosphatase; U73122, 1-[6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl) amino)hexyl]-1H-pyrrole-2,5-dione; U73343, 1-[6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-2,5-pyrrolidinedione.

    • Received June 12, 2003.
    • Accepted August 8, 2003.
  • 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: 307 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 307, Issue 2
1 Nov 2003
  • 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.
Cross Talk between P2Y2 Nucleotide Receptors and CXC Chemokine Receptor 2 Resulting in Enhanced Ca2+ Signaling Involves Enhancement of Phospholipase C Activity and Is Enabled by Incremental Ca2+ Release in Human Embryonic Kidney Cells
(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 ArticleCELLULAR AND MOLECULAR

Cross Talk between P2Y2 Nucleotide Receptors and CXC Chemokine Receptor 2 Resulting in Enhanced Ca2+ Signaling Involves Enhancement of Phospholipase C Activity and Is Enabled by Incremental Ca2+ Release in Human Embryonic Kidney Cells

Tim D. Werry, Graeme F. Wilkinson and Gary B. Willars
Journal of Pharmacology and Experimental Therapeutics November 1, 2003, 307 (2) 661-669; DOI: https://doi.org/10.1124/jpet.103.055632

Citation Manager Formats

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

Share
Research ArticleCELLULAR AND MOLECULAR

Cross Talk between P2Y2 Nucleotide Receptors and CXC Chemokine Receptor 2 Resulting in Enhanced Ca2+ Signaling Involves Enhancement of Phospholipase C Activity and Is Enabled by Incremental Ca2+ Release in Human Embryonic Kidney Cells

Tim D. Werry, Graeme F. Wilkinson and Gary B. Willars
Journal of Pharmacology and Experimental Therapeutics November 1, 2003, 307 (2) 661-669; DOI: https://doi.org/10.1124/jpet.103.055632
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

  • Chlorogenic Acid Inhibits Breast Cancer Metastasis
  • SNAP25 and mGluRs Control Pathological Tau Release
  • N-Stearoylethanolamine Inhibits Platelet Reactivity
Show more Cellular and Molecular

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