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
OtherPROSTAGLANDINS, LEUKOTRIENES AND OTHER EICOSANOIDS

Generation of the Isoprostane 8-Epi-prostaglandin F2α In Vitro and In Vivo via the Cyclooxygenases

Thomas Klein, Felix Reutter, Horst Schweer, Hannsjörg W. Seyberth and Rolf M. Nüsing
Journal of Pharmacology and Experimental Therapeutics September 1997, 282 (3) 1658-1665;
Thomas Klein
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Felix Reutter
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Horst Schweer
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hannsjörg W. Seyberth
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rolf M. Nüsing
  • 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

F2-Isoprostanes are isomers of the prostaglandin PGF2α. At least one compound of this group, 8-epi-PGF2α, exhibits biological activity, and therefore special interest is focused on the mechanism of isoprostane formation: enzyme catalyzed or radical mediated. We analyzed the formation of isoprostanes in vitro and in vivo. In both systems, purified cyclooxygenase isoenzymes and cell models specific for the cyclooxygenase isoenzymes, 8-epi-PGF2α formation could be totally suppressed by cyclooxygenase inhibitors. Indomethacin inhibited concentration-dependent 8-epi-PGF2α formation in platelets stimulated with calcium ionophore, arachidonic acid or thrombin. Nordihydroguaiaretic acid, an antioxidant, blocked isoprostane formation with a similar IC50 value as thromboxane B2 synthesis, pointing toward cyclooxygenase as the primary target of inhibition. Based on the turnover number, cyclooxygenase-2 formed higher levels of 8-epi-PGF2α than cyclooxygenase-1. Endogenous 8-epi-PGF2α production in rat mesangial cells correlated well with the mRNA and protein expression of cyclooxygenase-2 during interleukin-1 induction. However, in contrast to human platelets, which produced different forms of isoprostanes, rat mesangial cells appeared to form only 8-epi-PGF2α. Further, this indicates that mesangial cells may represent a cellular origin for renal 8-epi-PGF2αformation. Next, we analyzed the formation of isoprostanes in humans. A direct correlation was observed between indomethacin treatment and the decrease in 8-epi-PGF2α and isoprostane levels, but compared with other prostanoids the inhibition was less pronounced. In summary, based on the in vitro studies, a clear cyclooxygenase-dependent formation of isoprostanes, especially 8-epi-PGF2α, was observed. However, in vivoadditional formation via cyclooxygenase enzyme-independent mechanisms is likely.

Footnotes

  • Send reprint requests to: Dr. Rolf M. Nüsing, Department of Pediatrics, Philipps University of Marburg, 35033 Marburg, Germany. E-mail:nuesing{at}mailer.uni-marburg.de

  • ↵1 This work was supported by grants from the Deutsche Forschungsgemeinschaft (Nu 73/2–1, Se 263/11–1).

  • Abbreviations:
    PG
    prostaglandin
    COX
    cyclooxygenase
    NSAID
    nonsteroidal anti-inflammatory drug
    GC/MS/MS
    gas chromatography-tandem mass spectrometry
    RMC
    rat mesangial cells
    IL-1
    interleukin-1β
    TXB
    thromboxane
    HPS
    hyperprostaglandin syndrome
    RT
    reverse transcription
    PCR
    polymerase chain reaction
    • Received October 28, 1996.
    • Accepted May 5, 1997.
  • 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
Vol. 282, Issue 3
1 Sep 1997
  • Table of Contents
  • 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.
Generation of the Isoprostane 8-Epi-prostaglandin F2α In Vitro and In Vivo via the Cyclooxygenases
(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
OtherPROSTAGLANDINS, LEUKOTRIENES AND OTHER EICOSANOIDS

Generation of the Isoprostane 8-Epi-prostaglandin F2α In Vitro and In Vivo via the Cyclooxygenases

Thomas Klein, Felix Reutter, Horst Schweer, Hannsjörg W. Seyberth and Rolf M. Nüsing
Journal of Pharmacology and Experimental Therapeutics September 1, 1997, 282 (3) 1658-1665;

Citation Manager Formats

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

Share
OtherPROSTAGLANDINS, LEUKOTRIENES AND OTHER EICOSANOIDS

Generation of the Isoprostane 8-Epi-prostaglandin F2α In Vitro and In Vivo via the Cyclooxygenases

Thomas Klein, Felix Reutter, Horst Schweer, Hannsjörg W. Seyberth and Rolf M. Nüsing
Journal of Pharmacology and Experimental Therapeutics September 1, 1997, 282 (3) 1658-1665;
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

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

Related Articles

Cited By...

More in this TOC Section

  • Biosynthesis of Sulfidopeptide Leukotrienes Via the Transfer of Leukotriene A4 from Polymorphonuclear Cells to Bovine Retinal Pericytes
  • The Preclinical Pharmacological Profile of the Potent and Selective Leukotriene B4 Antagonist CP-195543
  • NO-Independent Vasodilation to Acetylcholine in the Rat Isolated Kidney Utilizes a Charybdotoxin-Sensitive, Intermediate-Conductance Ca++-Activated K+ Channel
Show more PROSTAGLANDINS, LEUKOTRIENES AND OTHER EICOSANOIDS

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