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Lack of evidence for functional ADP-activated human P2X1 receptors supports a role for ATP during hemostasis and thrombosis.

Research output: Contribution to journalArticle

Author(s)

Catherine Vial, Samantha Jane Pitt, Jon A Roberts, Michael G Rolf, Martyn P Mahaut-Smith, Richard J Evans

School/Research organisations

Abstract

Purine nucleotides acting through P2 receptors play key roles in platelet signaling. The P2X1 receptor is an adenosine triphosphate (ATP)-gated ion channel that mediates a rapid calcium influx signal, but can also synergize with subsequent adenosine diphosphate (ADP)-evoked P2Y1 receptor-mediated responses and thus may contribute to platelet activation during hemostasis. Recent studies have shown that P2X1 receptors contribute to the formation of platelet thrombi, particularly under conditions of high shear stress. Based on intracellular Ca2+ measurements a previous report has suggested that a splice variant of the P2X1 receptor, P2X1del, is expressed in platelets and, in contrast to the full-length P2X1WT receptor, is activated by ADP. In the present study we show that the P2X1del receptor fails to form functional ion channels and is below the limit of detection in human platelets. Furthermore, ADP does not contribute to the rapid ionotropic P2X receptor-mediated response in platelets. These results support the notion that ATP is the principal physiologic agonist at P2X1 receptors and that it plays a role in the activation of platelets.

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Details

Original languageEnglish
Pages (from-to)3646-51
JournalBlood
Volume102
Issue number10
DOIs
Publication statusPublished - 2003

    Research areas

  • P2 receptors, Purine Nucleotides, Platelets, Hemostasis

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