{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nP2X1 (P2RX1) is an ATP‐gated cation channel that is broadly expressed in diverse cell types where it plays a pivotal role in mediating rapid Ca²⁺ influx and initiating downstream cellular responses. In T lymphocytes, for example, stimulation of the T‐cell receptor drives the rapid translocation of P2X1 receptors to the immune synapse, enhancing Ca²⁺ entry and thereby contributing to signal amplification and T‐cell activation. In the megakaryocytic lineage and platelets, P2X1 activation under conditions such as low‐dose collagen stimulation or high shear stress triggers fast and reversible changes in intracellular Ca²⁺ levels that promote shape change, granule secretion, and aggregation—processes critical for hemostasis and thrombosis. Moreover, a distinct expression of P2X1 receptors in smooth muscle and skeletal muscle (including localization to the sarcolemma) further implicates this receptor in regulating vascular tone and blood flow."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, extensive structure–function studies have delineated key residues and domains within the P2X1 receptor that determine its ATP‐binding affinity, gating kinetics, and sensitivity to antagonists. Mutagenesis experiments have identified conserved aromatic and charged residues in the extracellular ligand‐binding loop that coordinate the adenine moiety of ATP and are essential for channel activation and rapid desensitization. Furthermore, P2X1 receptors are dynamically regulated by their association with cholesterol‐rich lipid rafts and the cytoskeletal network—interactions that stabilize receptor conformation and facilitate localized signal transduction. Additional studies have revealed species‐specific determinants and critical intracellular domains that modulate receptor recovery, underscoring the importance of receptor recycling and posttranslational modifications in governing P2X1‐mediated responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "26"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its immediate biophysical properties, P2X1 receptor function is further fine‐tuned by regulatory mechanisms that control its membrane trafficking, stability, and interaction with accessory proteins. Receptor recycling, modulated by the cytoskeleton and chaperones such as HSP90, is critical for maintaining P2X1 responsiveness during repetitive stimulation. In addition, altered expression or posttranslational modifications of P2X1 have been implicated in diverse pathophysiological contexts—including the regulation of renal microvascular tone, uterine and bladder contractility, as well as the control of immune cell functions such as macrophage apoptosis and eosinophil adhesion in inflammatory states or leukemia. These findings underscore the receptor’s versatile contribution to intercellular communication and its potential as a therapeutic target in disorders ranging from thrombosis and hypertension to immune and inflammatory diseases."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "27", "end_ref": "49"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ross Corriden, Paul A Insel "}, {"type": "b", "children": [{"type": "t", "text": "Basal release of ATP: an autocrine-paracrine mechanism for cell regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Signal (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scisignal.3104re1"}], "href": "https://doi.org/10.1126/scisignal.3104re1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20068232"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20068232"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Tobias Woehrle, Linda Yip, Abdallah Elkhal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pannexin-1 hemichannel-mediated ATP release together with P2X1 and P2X4 receptors regulate T-cell activation at the immune synapse."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2010-04-277707"}], "href": "https://doi.org/10.1182/blood-2010-04-277707"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20660288"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20660288"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Cécile Oury, Marijke J E Kuijpers, Emese Toth-Zsamboki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of the platelet P2X1 ion channel in transgenic mice generates a novel prothrombotic phenotype."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2002-10-3215"}], "href": "https://doi.org/10.1182/blood-2002-10-3215"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12521992"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12521992"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Stefan P Mortensen, José González-Alonso, Laurids T Bune, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ATP-induced vasodilation and purinergic receptors in the human leg: roles of nitric oxide, prostaglandins, and adenosine."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Regul Integr Comp Physiol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpregu.90822.2008"}], "href": "https://doi.org/10.1152/ajpregu.90822.2008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19118095"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19118095"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Catherine Vial, Richard J Evans "}, {"type": "b", "children": [{"type": "t", "text": "Disruption of lipid rafts inhibits P2X1 receptor-mediated currents and arterial vasoconstriction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M504256200"}], "href": "https://doi.org/10.1074/jbc.M504256200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16006561"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16006561"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Cécile Oury, Emese Toth-Zsamboki, Jos Vermylen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "P2X(1)-mediated activation of extracellular signal-regulated kinase 2 contributes to platelet secretion and aggregation induced by collagen."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2002-03-0812"}], "href": "https://doi.org/10.1182/blood-2002-03-0812"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12239162"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12239162"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "C Oury, E Toth-Zsamboki, C Thys, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The ATP-gated P2X1 ion channel acts as a positive regulator of platelet responses to collagen."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thromb Haemost (2001)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11816716"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11816716"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "K Wareham, C Vial, R C E Wykes, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional evidence for the expression of P2X1, P2X4 and P2X7 receptors in human lung mast cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Pharmacol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1476-5381.2009.00287.x"}], "href": "https://doi.org/10.1111/j.1476-5381.2009.00287.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19552691"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19552691"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Emese Toth-Zsamboki, Cécile Oury, Heidi Cornelissen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "P2X1-mediated ERK2 activation amplifies the collagen-induced platelet secretion by enhancing myosin light chain kinase activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M308452200"}], "href": "https://doi.org/10.1074/jbc.M308452200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14500714"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14500714"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Cécile Oury, Elsie Sticker, Heidi Cornelissen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ATP augments von Willebrand factor-dependent shear-induced platelet aggregation through Ca2+-calmodulin and myosin light chain kinase activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M402032200"}], "href": "https://doi.org/10.1074/jbc.M402032200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15087444"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15087444"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Michael G Rolf, Martyn P Mahaut-Smith "}, {"type": "b", "children": [{"type": "t", "text": "Effects of enhanced P2X1 receptor Ca2+ influx on functional responses in human platelets."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thromb Haemost (2002)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12353081"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12353081"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Magnus Grenegård, Karin Vretenbrant-Oberg, Martina Nylander, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The ATP-gated P2X1 receptor plays a pivotal role in activation of aspirin-treated platelets by thrombin and epinephrine."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M800358200"}], "href": "https://doi.org/10.1074/jbc.M800358200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18480058"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18480058"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Jonathan A Roberts, Richard J Evans "}, {"type": "b", "children": [{"type": "t", "text": "ATP binding at human P2X1 receptors. Contribution of aromatic and basic amino acids revealed using mutagenesis and partial agonists."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M308964200"}], "href": "https://doi.org/10.1074/jbc.M308964200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14699168"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14699168"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Christelle Lecut, Kim Frederix, Daniel M Johnson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "P2X1 ion channels promote neutrophil chemotaxis through Rho kinase activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.0804007"}], "href": "https://doi.org/10.4049/jimmunol.0804007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19635923"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19635923"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Jonathan A Roberts, Rebecca C Allsopp, Sam El Ajouz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Agonist binding evokes extensive conformational changes in the extracellular domain of the ATP-gated human P2X1 receptor ion channel."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1201872109"}], "href": "https://doi.org/10.1073/pnas.1201872109"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22393010"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22393010"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "H Kälvegren, C Skoglund, C Helldahl, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Toll-like receptor 2 stimulation of platelets is mediated by purinergic P2X1-dependent Ca2+ mobilisation, cyclooxygenase and purinergic P2Y1 and P2Y12 receptor activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thromb Haemost (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1160/TH09-07-0442"}], "href": "https://doi.org/10.1160/TH09-07-0442"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20024498"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20024498"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Rebecca C Allsopp, Ulyana Lalo, Richard J Evans "}, {"type": "b", "children": [{"type": "t", "text": "Lipid raft association and cholesterol sensitivity of P2X1-4 receptors for ATP: chimeras and point mutants identify intracellular amino-terminal residues involved in lipid regulation of P2X1 receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.148940"}], "href": "https://doi.org/10.1074/jbc.M110.148940"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20699225"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20699225"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Mufeng Li, Shai D Silberberg, Kenton J Swartz "}, {"type": "b", "children": [{"type": "t", "text": "Subtype-specific control of P2X receptor channel signaling by ATP and Mg2+."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1308088110"}], "href": "https://doi.org/10.1073/pnas.1308088110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23959888"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23959888"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Pia Thaning, Laurids T Bune, Ylva Hellsten, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Attenuated purinergic receptor function in patients with type 2 diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db09-1068"}], "href": "https://doi.org/10.2337/db09-1068"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19808895"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19808895"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Rebecca C Allsopp, Sam El Ajouz, Ralf Schmid, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cysteine scanning mutagenesis (residues Glu52-Gly96) of the human P2X1 receptor for ATP: mapping agonist binding and channel gating."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.260364"}], "href": "https://doi.org/10.1074/jbc.M111.260364"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21690089"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21690089"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "J A Erhardt, J R Toomey, S A Douglas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "P2X1 stimulation promotes thrombin receptor-mediated platelet aggregation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thromb Haemost (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1538-7836.2006.01849.x"}], "href": "https://doi.org/10.1111/j.1538-7836.2006.01849.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16634759"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16634759"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Catherine Vial, C Y Eleanor Fung, Alison H Goodall, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential sensitivity of human platelet P2X1 and P2Y1 receptors to disruption of lipid rafts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2006.02.174"}], "href": "https://doi.org/10.1016/j.bbrc.2006.02.174"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16546137"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16546137"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "C Lecut, C Faccinetto, C Delierneux, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ATP-gated P2X1 ion channels protect against endotoxemia by dampening neutrophil activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thromb Haemost (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1538-7836.2011.04606.x"}], "href": "https://doi.org/10.1111/j.1538-7836.2011.04606.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22212928"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22212928"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Catherine Vial, Samantha J Pitt, Jon Roberts, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lack of evidence for functional ADP-activated human P2X1 receptors supports a role for ATP during hemostasis and thrombosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2003-06-1963"}], "href": "https://doi.org/10.1182/blood-2003-06-1963"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12907444"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12907444"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Joan A Sim, Helen E Broomhead, R Alan North "}, {"type": "b", "children": [{"type": "t", "text": "Ectodomain lysines and suramin block of P2X1 receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M802523200"}], "href": "https://doi.org/10.1074/jbc.M802523200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18765669"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18765669"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "J A Erhardt, K Pillarisetti, J R Toomey "}, {"type": "b", "children": [{"type": "t", "text": "Potentiation of platelet activation through the stimulation of P2X1 receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thromb Haemost (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1046/j.1538-7836.2003.00453.x"}], "href": "https://doi.org/10.1046/j.1538-7836.2003.00453.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14675100"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14675100"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Lingwei Wang, Maria Andersson, Lena Karlsson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased mitogenic and decreased contractile P2 receptors in smooth muscle cells by shear stress in human vessels with intact endothelium."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arterioscler Thromb Vasc Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/01.ATV.0000080350.37408.5A"}], "href": "https://doi.org/10.1161/01.ATV.0000080350.37408.5A"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12791671"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12791671"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Ulyana Lalo, Rebecca C Allsopp, Martyn P Mahaut-Smith, et al. "}, {"type": "b", "children": [{"type": "t", "text": "P2X1 receptor mobility and trafficking; regulation by receptor insertion and activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurochem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1471-4159.2010.06730.x"}], "href": "https://doi.org/10.1111/j.1471-4159.2010.06730.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20374431"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20374431"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Ulyana Lalo, Sarah Jones, Jonathan A Roberts, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Heat shock protein 90 inhibitors reduce trafficking of ATP-gated P2X1 receptors and human platelet responsiveness."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.376566"}], "href": "https://doi.org/10.1074/jbc.M112.376566"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22851178"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22851178"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Zhengrong Guan, Edward W Inscho "}, {"type": "b", "children": [{"type": "t", "text": "Role of adenosine 5'-triphosphate in regulating renal microvascular function and in hypertension."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hypertension (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/HYPERTENSIONAHA.110.155952"}], "href": "https://doi.org/10.1161/HYPERTENSIONAHA.110.155952"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21768526"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21768526"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Lele Jiang, Michelle Bardini, Anne Keogh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "P2X1 receptors are closely associated with connexin 43 in human ventricular myocardium."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cardiol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ijcard.2003.11.036"}], "href": "https://doi.org/10.1016/j.ijcard.2003.11.036"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15686781"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15686781"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "C Oury, K Daenens, H Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ERK2 activation in arteriolar and venular murine thrombosis: platelet receptor GPIb vs. P2X."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thromb Haemost (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1538-7836.2006.01745.x"}], "href": "https://doi.org/10.1111/j.1538-7836.2006.01745.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16420578"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16420578"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Ulyana Lalo, Jonathan A Roberts, Richard J Evans "}, {"type": "b", "children": [{"type": "t", "text": "Identification of human P2X1 receptor-interacting proteins reveals a role of the cytoskeleton in receptor regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.253153"}], "href": "https://doi.org/10.1074/jbc.M111.253153"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21757694"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21757694"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Helen R Digby, Jonathan A Roberts, Michael J Sutcliffe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Contribution of conserved glycine residues to ATP action at human P2X1 receptors: mutagenesis indicates that the glycine at position 250 is important for channel function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurochem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1471-4159.2005.03494.x"}], "href": "https://doi.org/10.1111/j.1471-4159.2005.03494.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16236030"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16236030"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "C Y Eleanor Fung, Charles A Brearley, Richard W Farndale, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A major role for P2X1 receptors in the early collagen-evoked intracellular Ca2+ responses of human platelets."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thromb Haemost (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1160/TH04-11-0732"}], "href": "https://doi.org/10.1160/TH04-11-0732"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16113781"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16113781"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Wendy Chen-Nee Chua, Lu Liu, Kylie J Mansfield, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Age-related changes of P2X(1) receptor mRNA in the bladder detrusor from men with and without bladder outlet obstruction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Gerontol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.exger.2007.02.003"}], "href": "https://doi.org/10.1016/j.exger.2007.02.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17399929"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17399929"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Fiona R Ray, Kate H Moore, Mitchell A Hansen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of purinergic P2X receptor innervation in human detrusor and subepithelium from adults with sensory urgency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Tissue Res (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00441-003-0788-z"}], "href": "https://doi.org/10.1007/s00441-003-0788-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14557870"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14557870"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Hong Huo, Alistair G Fryatt, Louise K Farmer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mapping the binding site of the P2X receptor antagonist PPADS reveals the importance of orthosteric site charge and the cysteine-rich head region."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA118.003737"}], "href": "https://doi.org/10.1074/jbc.RA118.003737"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29997254"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29997254"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Rebecca C Allsopp, Louise K Farmer, Alistair G Fryatt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "P2X receptor chimeras highlight roles of the amino terminus to partial agonist efficacy, the carboxyl terminus to recovery from desensitization, and independent regulation of channel transitions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.464651"}], "href": "https://doi.org/10.1074/jbc.M113.464651"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23740251"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23740251"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "M T Harper, M J Mason, S O Sage, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phorbol ester-evoked Ca2+ signaling in human platelets is via autocrine activation of P(2X1) receptors, not a novel non-capacitative Ca2+ entry."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thromb Haemost (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1538-7836.2010.03867.x"}], "href": "https://doi.org/10.1111/j.1538-7836.2010.03867.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20345709"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20345709"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "Airat U Ziganshin, Alexander P Zaitcev, Albir A Khasanov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Term-dependency of P2 receptor-mediated contractile responses of isolated human pregnant uterus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Obstet Gynecol Reprod Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejogrb.2005.11.018"}], "href": "https://doi.org/10.1016/j.ejogrb.2005.11.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16359770"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16359770"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "Li-Juan Zhou, Min Chen, Santhosh Puthiyakunnon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Toxoplasma gondii ROP18 inhibits human glioblastoma cell apoptosis through a mitochondrial pathway by targeting host cell P2X1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Parasit Vectors (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13071-019-3529-1"}], "href": "https://doi.org/10.1186/s13071-019-3529-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31164145"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31164145"}]}, {"type": "r", "ref": 43, "children": [{"type": "t", "text": "Katia Varani, Monica De Mattei, Fabrizio Vincenzi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "P2X(1) and P2X(3) purinergic receptors differentially modulate the inflammatory response in human osteoarthritic synovial fibroblasts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Physiol Biochem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000276565"}], "href": "https://doi.org/10.1159/000276565"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20110693"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20110693"}]}, {"type": "r", "ref": 44, "children": [{"type": "t", "text": "Emese Toth-Zsamboki, Cecile Oury, Hiroyuki Watanabe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The intracellular tyrosine residues of the ATP-gated P2X(1) ion channel are essential for its function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0014-5793(02)02987-3"}], "href": "https://doi.org/10.1016/s0014-5793(02"}, {"type": "t", "text": "02987-3) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12135734"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12135734"}]}, {"type": "r", "ref": 45, "children": [{"type": "t", "text": "Jonathan A Roberts, Andrew R Bottrill, Sharad Mistry, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mass spectrometry analysis of human P2X1 receptors; insight into phosphorylation, modelling and conformational changes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurochem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jnc.12012"}], "href": "https://doi.org/10.1111/jnc.12012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22971236"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22971236"}]}, {"type": "r", "ref": 46, "children": [{"type": "t", "text": "Eydie M Vargas-Martínez, Karen S Gómez-Coronado, Rosa Espinosa-Luna, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional expression of P2X1, P2X4 and P2X7 purinergic receptors in human monocyte-derived macrophages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Pharmacol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejphar.2020.173460"}], "href": "https://doi.org/10.1016/j.ejphar.2020.173460"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32805257"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32805257"}]}, {"type": "r", "ref": 47, "children": [{"type": "t", "text": "Claire M Nichols, Oleksandr V Povstyan, Anthony P Albert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Vascular smooth muscle cells from small human omental arteries express P2X1 and P2X4 receptor subunits."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Purinergic Signal (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11302-014-9415-6"}], "href": "https://doi.org/10.1007/s11302-014-9415-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24845338"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24845338"}]}, {"type": "r", "ref": 48, "children": [{"type": "t", "text": "Adam Wright, Martyn Mahaut-Smith, Fiona Symon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Impaired P2X1 Receptor-Mediated Adhesion in Eosinophils from Asthmatic Patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1501585"}], "href": "https://doi.org/10.4049/jimmunol.1501585"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27183585"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27183585"}]}, {"type": "r", "ref": 49, "children": [{"type": "t", "text": "Shayan Chen, Wenli Feng, Xiao Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional expression of P2X family receptors in macrophages is affected by microenvironment in mouse T cell acute lymphoblastic leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2014.03.048"}], "href": "https://doi.org/10.1016/j.bbrc.2014.03.048"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24661878"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24661878"}]}]}]}