The P2 Receptors in Platelet Function

Béatrice Hechler; Marco Cattaneo; Christian Gachet

doi:10.1055/s-2005-869520

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2005; 31(2): 150-161
DOI: 10.1055/s-2005-869520

The P2 Receptors in Platelet Function

Béatrice Hechler¹ ^, ² , Marco Cattaneo³ , Christian Gachet²

¹Researcher, Etablissement Français du Sang-Alsace, Strasbourg Cedex, France
²INSERM U.311, Etablissement Français du Sang-Alsace, Strasbourg Cedex, France
³Unit of Hematology and Thrombosis, Ospedale San Paolo, DMCO, University of Milan, Milan, Italy

Abstract

ABSTRACT

After vessel wall injury, platelets adhere to the exposed subendothelium, are activated, and release mediators such as thromboxane A₂ (TXA₂) and nucleotides stored at very high concentration in the so-called dense granules. Among other soluble agents, released nucleotides act in a positive feedback mechanism to cause further platelet activation and amplify platelet responses induced by agents such as thrombin or collagen. Adenine nucleotides act on platelets through three distinct P2 receptors: two are G protein-coupled adenosine diphosphate (ADP) receptors, namely the P2Y₁ and P2Y₁₂ receptor subtypes; the P2X₁ receptor ligand-gated cation channel is activated by adenosine triphosphate (ATP). The P2Y₁ receptor initiates platelet aggregation but is not sufficient for a full platelet aggregation in response to ADP, whereas the P2Y₁₂ receptor is responsible for completion of the aggregation to ADP. This receptor, the molecular target of the antithrombotic drug clopidogrel, is responsible for most of the potentiating effects of ADP when platelets are stimulated by agents such as thrombin, collagen, or immune complexes. The P2X₁ receptor is involved in platelet shape change and in activation by collagen under shear conditions. Each of these receptors is coupled to specific signal transduction pathways in response to ADP or ATP and is differentially involved in all of the sequential events involved in platelet function and hemostasis. As such, they represent potential targets for antithrombotic drugs.

KEYWORDS

Signal transduction - hemostasis - nucleotides - thrombosis

Full Text

References

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Dr. Christian Gachet

Inserm, Institut national de la sante et de la recherche medicale, Etablissement Francais du Sang-Alsace

10, Rue Spielmann, BP 36-67065 Strasbourg Cedex, France

Email: Christian.gachet@efs-alsace.fr