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20 - Platelet signalling: cAMP and cGMP

from PART I - PHYSIOLOGY

Published online by Cambridge University Press:  10 May 2010

James L. Daniel
Affiliation:
Department of Pharmacology and Sol Sherry Thrombosis Research Center, Temple University Medical School Philadelphia, USA
Barrie Ashby
Affiliation:
Department of Pharmacology and Sol Sherry Thrombosis Research Center, Temple University Medical School Philadelphia, USA
Fabio M. Pulcinelli
Affiliation:
Department of Experimental Medicine and Pathology, University La Sapienza, Rome, Italy
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

History

The first report that cyclic AMP had an effect on platelets came from Marcus and Zucker, who showed that dibutiryl cyclic AMP, a cell permeant cyclic AMP analogue, inhibited platelet aggregation. Ardlie et al. showed that methyl xanthines, which inhibit cyclic AMP phosphodiesterase and hence elevate cyclic AMP levels, also inhibit platelet aggregation and proposed that cyclic AMP is an important mediator of platelet function. In 1969, several groups of investigators reported that the level of platelet cyclic AMP regulated platelet function and showed that both platelet agonists and antagonists could affect the intraplatelet concentration of cyclic AMP. Salzman suggested that cyclic AMP might be the ultimate mediator of platelet activation in that agents that inhibited aggregation increased cyclic AMP, while agents that activated platelets did so by lowering the basal level of cyclic AMP. However, the idea that agonists activate platelets by lowering basal cyclic AMP was convincingly refuted by Haslam et al.

Elevated levels of cyclic GMP also inhibit platelet activation and platelet activators elevate cyclic GMP. However, the latter effect has been shown to be a consequence of aggregation and does not occur during other forms of platelet activation. A schematic summary of the information in this review is shown in Fig. 20.1.

Platelet receptors coupled to adenylyl cyclase activation

Prostaglandins that elevate cyclic AMP levels are potent inhibitors of platelet activation. Adenosine acts through the A2A receptor to activate adenylyl cyclase.

Type
Chapter
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Platelets in Thrombotic and Non-Thrombotic Disorders
Pathophysiology, Pharmacology and Therapeutics
, pp. 290 - 303
Publisher: Cambridge University Press
Print publication year: 2002

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  • Platelet signalling: cAMP and cGMP
    • By James L. Daniel, Department of Pharmacology and Sol Sherry Thrombosis Research Center, Temple University Medical School Philadelphia, USA, Barrie Ashby, Department of Pharmacology and Sol Sherry Thrombosis Research Center, Temple University Medical School Philadelphia, USA, Fabio M. Pulcinelli, Department of Experimental Medicine and Pathology, University La Sapienza, Rome, Italy
  • 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/CBO9780511545283.021
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  • Platelet signalling: cAMP and cGMP
    • By James L. Daniel, Department of Pharmacology and Sol Sherry Thrombosis Research Center, Temple University Medical School Philadelphia, USA, Barrie Ashby, Department of Pharmacology and Sol Sherry Thrombosis Research Center, Temple University Medical School Philadelphia, USA, Fabio M. Pulcinelli, Department of Experimental Medicine and Pathology, University La Sapienza, Rome, Italy
  • 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/CBO9780511545283.021
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 signalling: cAMP and cGMP
    • By James L. Daniel, Department of Pharmacology and Sol Sherry Thrombosis Research Center, Temple University Medical School Philadelphia, USA, Barrie Ashby, Department of Pharmacology and Sol Sherry Thrombosis Research Center, Temple University Medical School Philadelphia, USA, Fabio M. Pulcinelli, Department of Experimental Medicine and Pathology, University La Sapienza, Rome, Italy
  • 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/CBO9780511545283.021
Available formats
×