The P2X1 receptor and platelet function

Martyn P. Mahaut-Smith, Sarah Jones, Richard J. Evans

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Extracellular nucleotides are ubiquitous signalling molecules, acting via the P2 class of surface receptors. Platelets express three P2 receptor subtypes, ADP-dependent P2Y1 and P2Y12 G-protein-coupled receptors and the ATP-gated P2X1 non-selective cation channel. Platelet P2X1 receptors can generate significant increases in intracellular Ca 2+, leading to shape change, movement of secretory granules and low levels of α IIbβ 3 integrin activation. P2X1 can also synergise with several other receptors to amplify signalling and functional events in the platelet. In particular, activation of P2X1 receptors by ATP released from dense granules amplifies the aggregation responses to low levels of the major agonists, collagen and thrombin. In vivo studies using transgenic murine models show that P2X1 receptors amplify localised thrombosis following damage of small arteries and arterioles and also contribute to thromboembolism induced by intravenous co-injection of collagen and adrenaline. In vitro, under flow conditions, P2X1 receptors contribute more to aggregate formation on collagen-coated surfaces as the shear rate is increased, which may explain their greater contribution to localised thrombosis in arterioles compared to venules within in vivo models. Since shear increases substantially near sites of stenosis, anti-P2X1 therapy represents a potential means of reducing thrombotic events at atherosclerotic plaques. © 2011 The Author(s).
    Original languageEnglish
    Pages (from-to)341-356
    Number of pages15
    JournalPurinergic Signalling
    Volume7
    Issue number3
    DOIs
    Publication statusPublished - Sep 2011

    Keywords

    • ATP
    • P2X1
    • Platelets
    • Shear
    • Thromboembolism
    • Thrombosis

    Fingerprint

    Dive into the research topics of 'The P2X1 receptor and platelet function'. Together they form a unique fingerprint.

    Cite this