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 ArticleORIGINAL ARTICLE

The Aminosteroid Phospholipase C Antagonist U-73122 (1-[6-[[17-β-3-Methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione) Potently Inhibits Human 5-Lipoxygenase in Vivo and in Vitro

Christian Feißt, Dana Albert, Dieter Steinhilber and Oliver Werz
Molecular Pharmacology May 2005, 67 (5) 1751-1757; DOI: https://doi.org/10.1124/mol.105.011007
Christian Feißt
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dana Albert
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dieter Steinhilber
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Oliver Werz
  • 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

U-73122 (1-[6-[[17-β-3-methoxyestra-1,3,5(10)-trien-17-yl]amino] hexyl]-1H-pyrrole-2,5-dione) is a widely used antagonist of phosphoinositide-specific phospholipase C (PLC) and is frequently used to define a role of PLC in receptor-mediated elevation of intracellular calcium concentration ([Ca2+]i). In human polymorphonuclear leukocytes (PMNLs), U-73122 inhibited increases in [Ca2+]i induced by G protein-coupled receptor (GPCR) agonists (N-formyl-methionyl-leucyl-phenylalanine or platelet-activating factor; IC50 of ≈2 to 4 μM), but it failed to suppress responses induced by ionomycin or thapsigargin. 5-Lipoxygenase (5-LO) is a Ca2+-regulated enzyme that can be activated in leukocytes by stimuli that elevate [Ca2+]i. Attempts to investigate the involvement of PLC in cellular 5-LO activation revealed that U-73122 suppresses 5-LO product synthesis regardless of the stimulus and independently of Ca2+. Thus, U-73122 blocked 5-LO product synthesis induced by cell stress, involving 5-LO phosphorylation pathways in the absence of Ca2+ with an IC50 of ≈2 μM. Direct inhibition of 5-LO by U-73122 was evident in PMNL homogenates (IC50 of ≈2.4 μM), and isolated human recombinant 5-LO enzyme was potently inhibited by U-73122 (IC50 of ≈30 nM). Thiols (glutathione) strongly blunted the effect of U-73122 on isolated 5-LO. On the other hand, depletion of cellular thiols by N-ethylmaleimide strongly increased the efficacy of U-73122 to inhibit 5-LO in intact cells or corresponding homogenates, suggesting that U-73122 may interfere with sulfhydryl groups on 5-LO. Since 5-LO products induce increases in [Ca2+]i via GPCRs, caution should be used when interpreting data where U-73122 is used as tool to determine a direct role of PLC in receptor-mediated Ca2+ mobilization.

  • Received January 6, 2005.
  • Accepted January 31, 2005.
  • 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: 67 (5)
Molecular Pharmacology
Vol. 67, Issue 5
1 May 2005
  • 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.
The Aminosteroid Phospholipase C Antagonist U-73122 (1-[6-[[17-β-3-Methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione) Potently Inhibits Human 5-Lipoxygenase in Vivo and in Vitro
(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 ArticleORIGINAL ARTICLE

The Aminosteroid Phospholipase C Antagonist U-73122 (1-[6-[[17-β-3-Methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione) Potently Inhibits Human 5-Lipoxygenase in Vivo and in Vitro

Christian Feißt, Dana Albert, Dieter Steinhilber and Oliver Werz
Molecular Pharmacology May 1, 2005, 67 (5) 1751-1757; DOI: https://doi.org/10.1124/mol.105.011007

Citation Manager Formats

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

Share
Research ArticleORIGINAL ARTICLE

The Aminosteroid Phospholipase C Antagonist U-73122 (1-[6-[[17-β-3-Methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione) Potently Inhibits Human 5-Lipoxygenase in Vivo and in Vitro

Christian Feißt, Dana Albert, Dieter Steinhilber and Oliver Werz
Molecular Pharmacology May 1, 2005, 67 (5) 1751-1757; DOI: https://doi.org/10.1124/mol.105.011007
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
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • The 73-kDa Heat Shock Cognate Protein Is a CXCR4 Binding Protein that Regulates the Receptor Endocytosis and the Receptor-Mediated Chemotaxis
  • Endogenous Regulator of G-Protein Signaling Proteins Regulate the Kinetics of Gαq/11-Mediated Modulation of Ion Channels in Central Nervous System Neurons
  • A Novel Cyclohexene Derivative, Ethyl (6R)-6-[N-(2-Chloro-4-fluorophenyl)sulfamoyl]cyclohex-1-ene-1-carboxylate (TAK-242), Selectively Inhibits Toll-Like Receptor 4-Mediated Cytokine Production through Suppression of Intracellular Signaling
Show more ORIGINAL 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 © 2022 by the American Society for Pharmacology and Experimental Therapeutics