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8 - Platelet receptors for thrombin

from PART I - PHYSIOLOGY

Published online by Cambridge University Press:  10 May 2010

Lawrence F. Brass
Affiliation:
Departments of Medicine and Pharmacology, and the Center for Experimental Therapeutics at the University of Pennsylvania, Philadelphia, USA
Marina Molino
Affiliation:
Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy
Peter J. O'Brien
Affiliation:
Departments of Medicine and Pharmacology, and the Center for Experimental Therapeutics at the University of Pennsylvania, Philadelphia, USA
Mark Kahn
Affiliation:
Departments of Medicine and Pharmacology, and the Center for Experimental Therapeutics at the University of Pennsylvania, Philadelphia, USA
Paolo Gresele
Affiliation:
Università degli Studi di Perugia, Italy
Clive P. Page
Affiliation:
Sackler Institute of Pulmonary Pharmacology and Therapeutics, Guy's, King's and St Thomas' School of Biomedical Sciences, London
Valentin Fuster
Affiliation:
Mount Sinai Medical Center and School of Medicine, New York
Jos Vermylen
Affiliation:
Universiteitsbibliotheek-K.U., Leuven
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Summary

Introduction

Thrombin is one of the most potent agonists that platelets will encounter in vivo, but unlike most of the others it is a protease. For years after thrombin was shown to be a platelet activator as well as an effector in the clotting cascade, the precise mechanism by which it activates platelets remained obscure. Binding studies demonstrated high affinity interactions with several sites on the platelet surface, including glycoprotein (GP) Ibα, but efforts to establish that any of these constituted a receptor in the signalling sense were not entirely successful. Substrates on the platelet surface for proteolytic cleavage by thrombin were also identified, including GP V, but cleavage of these sites did not appear to be required for platelet activation by thrombin. Before discussing the receptors that have been identified, it is worth considering what some of the criteria might be for establishing a protein as a true signalling receptor for thrombin. Such criteria would include (i) demonstrating its presence on the platelet surface, (ii) showing that it was a substrate for thrombin or closely associated with a substrate for thrombin, (iii) demonstrating an association of the candidate receptor with mediators or effectors for intracellular signalling cascades, (iv) showing that expression of the candidate receptor could render a cell that was otherwise unresponsive to thrombin capable of responding, and (v) showing that blocking, dismantling or otherwise removing the candidate receptor would reduce platelet responses to thrombin.

Type
Chapter
Information
Platelets in Thrombotic and Non-Thrombotic Disorders
Pathophysiology, Pharmacology and Therapeutics
, pp. 113 - 126
Publisher: Cambridge University Press
Print publication year: 2002

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  • Platelet receptors for thrombin
    • By Lawrence F. Brass, Departments of Medicine and Pharmacology, and the Center for Experimental Therapeutics at the University of Pennsylvania, Philadelphia, USA, Marina Molino, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy, Peter J. O'Brien, Departments of Medicine and Pharmacology, and the Center for Experimental Therapeutics at the University of Pennsylvania, Philadelphia, USA, Mark Kahn, Departments of Medicine and Pharmacology, and the Center for Experimental Therapeutics at the University of Pennsylvania, Philadelphia, USA
  • Edited by Paolo Gresele, Università degli Studi di Perugia, Italy, Clive P. Page, Valentin Fuster, Jos Vermylen, Universiteitsbibliotheek-K.U., Leuven
  • Book: Platelets in Thrombotic and Non-Thrombotic Disorders
  • Online publication: 10 May 2010
  • Chapter DOI: https://doi.org/10.1017/CBO9780511545283.009
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  • Platelet receptors for thrombin
    • By Lawrence F. Brass, Departments of Medicine and Pharmacology, and the Center for Experimental Therapeutics at the University of Pennsylvania, Philadelphia, USA, Marina Molino, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy, Peter J. O'Brien, Departments of Medicine and Pharmacology, and the Center for Experimental Therapeutics at the University of Pennsylvania, Philadelphia, USA, Mark Kahn, Departments of Medicine and Pharmacology, and the Center for Experimental Therapeutics at the University of Pennsylvania, Philadelphia, USA
  • Edited by Paolo Gresele, Università degli Studi di Perugia, Italy, Clive P. Page, Valentin Fuster, Jos Vermylen, Universiteitsbibliotheek-K.U., Leuven
  • Book: Platelets in Thrombotic and Non-Thrombotic Disorders
  • Online publication: 10 May 2010
  • Chapter DOI: https://doi.org/10.1017/CBO9780511545283.009
Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

  • Platelet receptors for thrombin
    • By Lawrence F. Brass, Departments of Medicine and Pharmacology, and the Center for Experimental Therapeutics at the University of Pennsylvania, Philadelphia, USA, Marina Molino, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy, Peter J. O'Brien, Departments of Medicine and Pharmacology, and the Center for Experimental Therapeutics at the University of Pennsylvania, Philadelphia, USA, Mark Kahn, Departments of Medicine and Pharmacology, and the Center for Experimental Therapeutics at the University of Pennsylvania, Philadelphia, USA
  • Edited by Paolo Gresele, Università degli Studi di Perugia, Italy, Clive P. Page, Valentin Fuster, Jos Vermylen, Universiteitsbibliotheek-K.U., Leuven
  • Book: Platelets in Thrombotic and Non-Thrombotic Disorders
  • Online publication: 10 May 2010
  • Chapter DOI: https://doi.org/10.1017/CBO9780511545283.009
Available formats
×