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20 - Platelet signalling: cAMP and cGMP
- from PART I - PHYSIOLOGY
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- 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
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- Book:
- Platelets in Thrombotic and Non-Thrombotic Disorders
- Published online:
- 10 May 2010
- Print publication:
- 30 May 2002, pp 290-303
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- Chapter
- Export citation
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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.