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 Printable version |
Molecular identity of the platelet ADP receptors : physiology and pharmacology |
Hématologie. Volume 4, Number 2, 107-15, Mars-Avril 1998, Mini-revues et revues
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 Résumé
Article gratuit
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Author(s) : Christian Gachet, Jean-Pierre Cazenave |
Summary : Extracellular nucleotides interact with P2 receptors to regulate a broad range of physiological processes among which platelet aggregation. P2 receptors were divided into two main groups : the G protein coupled receptor or metabotropic superfamily termed P2Y and the ligand-gated ion channel or ionotropic receptor superfamily termed P2X. Platelet aggregation by ADP plays a key role in the development and extension of arterial thrombosis. Although ADP was the first low molecular weight platelet aggregating agent to be identified, the identity of a platelet specific ADP receptor was elusive for a long time. Such a receptor, unique in the field of P2 receptors, termed P2T, should be activated by ADP, ATP and related analogs being antagonists. In fact, two ADP receptors at least mediate the multiple effects of ADP on platelets : the P2Y1 receptor, also present on endothelial cells, which has been demonstrated to be an ADP receptor at which ATP and related triphosphate analogues are antagonists, probably responsible for platelet aggregation, and the P2X1 receptor, also present on vascular smooth muscle cells, responsible for the fast calcium entry. Multiple ecto-enzymes present on endothelial cells and on platelets are involved in the regulation of nucleotide concentration and thus participate in the thrombogenic state in the cardiovascular system. Hence at a site of vascular injury the purinergic system with its multiple receptors expressed on different cells participates, among other mechanisms, in the regulation of haemostasis. Moreover, the purinergic system regulates many other processes of cardiovascular physiology such as vascular tone, heart rate and contractility in which platelets may play a key role. The fact that the various tissues and cells involved in these processes share identical receptors raises the question of the selectivity of pharmacological interference. |
Keywords : purinergic receptors, P2T, P2X1, P2Y1, platelet aggregation, thrombosis. |
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