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

Interaction of a Thrombin Inhibitor and a Platelet GP IIb/IIIa Antagonist In Vivo: Evidence That Thrombin Mediates Platelet Aggregation and Subsequent Thromboxane A2 Formation During Coronary Thrombolysis

Domenico Pratico, Natalie P. Murphy and Desmond J. Fitzgerald
Journal of Pharmacology and Experimental Therapeutics June 1997, 281 (3) 1178-1185;
Domenico Pratico
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Natalie P. Murphy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Desmond J. Fitzgerald
  • 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 examined the effect of a specific thrombin inhibitor, Ro 46-6240, alone and combined with an antagonist of the platelet GP IIb/IIIa, Ro44-9883, on the response to tissue-type plasminogen activator in a canine model of thrombolysis. Platelet activity was determined by measuring the excretion of 2,3-dinor-thromboxane (TX)B2, an enzymatic metabolite of TXA2. Ro 46-6240 administered before tissue-type plasminogen activator induced a dose-dependent prolongation of the activated partial thromboplastin time and prothrombin time. The time to reperfusion decreased dose-dependently (P < .01) to 10 ± 6 min vs. 52 ± 5 min in controls. Ro 46-6240 also prevented reocclusion, which occurred in every case in control experiments. Urinary excretion of 2,3-dinor-TXB2 increased from 3 ± 1 to 37 ± 9 ng/mg creatinine in controls after reperfusion. This increase was reduced in a dose-dependent fashion by Ro 46-6240, such that at the highest dose, urinary 2,3-dinor-TXB2 after reperfusion was 5.6 ± 1 ng/mg creatinine. Similar functional and biochemical effects were seen when a subthreshold dose of Ro 46-6240 was combined with Ro 44-9883. At the dose used, Ro 44-9883 alone abolished platelet aggregation ex vivo but failed to modify the response to tissue-type plasminogen activator or the excretion of 2,3-dinor-TXB2 after reperfusion (51 ± 6 ng/mg creatinine, n = 3). However, the combination of Ro 44-9883 and Ro 46-6240 reduced the time to reperfusion (40 ± 8vs. 68 ± 15 min; n = 7, P < .05), prevented reocclusion and abolished the rise in urinary 2,3-dinor-TXB2 (5 ± 1 ng/mg creatinine,n = 4). These findings suggest that thrombin mediates platelet activation during coronary thrombolysis. The increased platelet activity results in platelet aggregation and a subsequent increase in TXA2 formation.

Footnotes

  • Send reprint requests to: Desmond Fitzgerald, Centre for Cardiovascular Science, Dept. of Clinical Pharmacology, Royal College of Surgeons in Ireland, St. Stephens Green, Dublin 2, Ireland.

  • ↵1 The work was supported by grants from the Wellcome Trust and the Irish Heart Foundation.

  • ↵2 Present address: Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania.

  • Abbreviations:
    TX
    thromboxane
    t-PA
    tissue-type plasminogen activator
    GP
    glycoprotein
    aPTT
    activated partial thromboplastin time
    PT
    prothrombin time
    • Received October 9, 1996.
    • Accepted February 24, 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. 281, Issue 3
1 Jun 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.
Interaction of a Thrombin Inhibitor and a Platelet GP IIb/IIIa Antagonist In Vivo: Evidence That Thrombin Mediates Platelet Aggregation and Subsequent Thromboxane A2 Formation During Coronary Thrombolysis
(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

Interaction of a Thrombin Inhibitor and a Platelet GP IIb/IIIa Antagonist In Vivo: Evidence That Thrombin Mediates Platelet Aggregation and Subsequent Thromboxane A2 Formation During Coronary Thrombolysis

Domenico Pratico, Natalie P. Murphy and Desmond J. Fitzgerald
Journal of Pharmacology and Experimental Therapeutics June 1, 1997, 281 (3) 1178-1185;

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

Interaction of a Thrombin Inhibitor and a Platelet GP IIb/IIIa Antagonist In Vivo: Evidence That Thrombin Mediates Platelet Aggregation and Subsequent Thromboxane A2 Formation During Coronary Thrombolysis

Domenico Pratico, Natalie P. Murphy and Desmond J. Fitzgerald
Journal of Pharmacology and Experimental Therapeutics June 1, 1997, 281 (3) 1178-1185;
Reddit logo Twitter logo Facebook 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

  • 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