title: Lack of evidence for functional ADP-activated human P2X1 receptors supports a role for ATP during hemostasis and thrombosis.
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.
authors.affiliation: Department of Cell Physiology and Pharmacology, University of Leicester, University Rd, Leicester LE1 9HN, United Kingdom.
authors.forename: Catherine
authors.initials: C
authors.lastname: Vial
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Pitt
authors.forename: Jon
authors.initials: J
authors.lastname: Roberts
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rolf
authors.forename: Martyn P
authors.initials: MP
authors.lastname: Mahaut-Smith
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Evans
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology / Q000502:physiology*; D017398:Alternative Splicing; D001792:Blood Platelets / Q000378:metabolism; D020013:Calcium Signaling; D002460:Cell Line; D004594:Electrophysiology; D006487:Hemostasis; D006801:Humans; D008565:Membrane Proteins; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D058469:Receptors, Purinergic P2X; D058925:Receptors, Purinergic P2Y12; D013927:Thrombosis / Q000209:etiology*; D014162:Transfection
chemical_list: D008565:Membrane Proteins; C548576:P2RY12 protein, human; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D058925:Receptors, Purinergic P2Y12; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate