Abstract
P2X1 receptors are ATP-gated channel demonstrated to be involved in multiple platelet responses, although in vitro analysis has been complicated by the effects of rapid desensitization. To further investigate potential roles of P2X1 receptors in platelet activation, the current study employed methods which maximally preserved P2X1 functionality. In preliminary in vivo studies, P2X1-deficiency reduced thrombus formation following the laser-induced, but not FeCl3-induced injury. Given the multiple potential mechanisms involved in thrombus formation in vivo, including tissue-factor/thrombin generation pathways, subsequent studies were designed to investigate the effects of P2X1 inhibition or stimulation on platelet activation in vitro; specifically, the interaction of P2X1 with thrombin receptor stimulation. Aggregation initiated by low/threshold levels of a protease-activated receptor (PAR)4 agonist was reduced in P2X1-deficient murine platelets, and inhibition of P2X1 in wild-type platelets similarly reduced PAR4-mediated aggregation. In human platelets, aggregation to low/threshold stimulation of PAR1 was inhibited with the P2X1 antagonist MRS2159. In addition, P2X1 stimulation primed human platelet responses, such that subsequ...Continue Reading
References
Feb 23, 1996·The Journal of Biological Chemistry·S J WoodR Wetzel
Oct 7, 1998·Physiology & Behavior·R A BaumanG J Kant
Sep 30, 1999·Nature Medicine·J E FabreB H Koller
Dec 22, 1999·The Journal of Clinical Investigation·C LéonC Gachet
Sep 6, 2000·Cell Calcium·S O SageJ W Heemskerk
Apr 17, 2001·Laboratory Investigation; a Journal of Technical Methods and Pathology·E Maurer-SpurejD V Devine
Jun 20, 2001·The Journal of Clinical Investigation·C J FosterM S Chintala
Jan 30, 2002·British Journal of Pharmacology·Catherine VialRichard J Evans
Sep 20, 2002·Blood·Cécile OuryMarc F Hoylaerts
Jan 11, 2003·Blood·Cécile OuryMarc F Hoylaerts
Apr 15, 2003·Toxicology and Applied Pharmacology·Tsung-Ming ShihJohn H McDonough
Jul 23, 2003·Journal of Thrombosis and Haemostasis : JTH·N LenainC Gachet
Aug 13, 2003·The Journal of Experimental Medicine·Béatrice HechlerChristian Gachet
Sep 23, 2003·The Journal of Biological Chemistry·Emese Toth-ZsambokiMarc F Hoylaerts
Dec 17, 2003·Journal of Thrombosis and Haemostasis : JTH·J A ErhardtJ R Toomey
Apr 17, 2004·The Journal of Biological Chemistry·Cécile OuryMarc F Hoylaerts
Jun 19, 2004·Platelets·Martyn P Mahaut-SmithRichard J Evans
Jul 29, 2004·Blood·Janet ChouBruce Furie
Mar 8, 2005·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Douglas G JohnsStephen A Douglas
Mar 29, 2005·The Journal of Pharmacology and Experimental Therapeutics·Béatrice HechlerChristian Gachet
Aug 23, 2005·Thrombosis and Haemostasis·C Y Eleanor FungMartyn P Mahaut-Smith
Citations
Apr 13, 2011·Purinergic Signalling·Martyn P Mahaut-SmithRichard J Evans
Oct 31, 2006·Photomedicine and Laser Surgery
Jul 5, 2013·PloS One·Jaione BurzacoAida Marino
Feb 4, 2014·Pathologie-biologie·R DarboussetC Dubois
May 27, 2009·Trends in Cardiovascular Medicine·C Y E FungMartyn P Mahaut-Smith
Jan 27, 2009·European Journal of Pharmacology·Douglas G JohnsMichael C Jaye
Mar 19, 2014·Thrombosis and Haemostasis·Z HuangH Hu
May 9, 2009·Journal of Thrombosis and Haemostasis : JTH·D Varga-SzaboB Nieswandt
Oct 25, 2006·Journal of Thrombosis and Haemostasis : JTH·B N KahnerS P Kunapuli
Mar 17, 2007·Journal of Thrombosis and Haemostasis : JTH·C Y E FungM P Mahaut-Smith
Jun 30, 2012·Journal of Thrombosis and Haemostasis : JTH·M P Mahaut-Smith
Mar 6, 2010·Platelets·Hu Hu, Marc F Hoylaerts
Aug 26, 2014·Blood·Roxane DarboussetChristophe Dubois
Oct 18, 2014·Blood·Donna S Woulfe
Feb 24, 2015·The Journal of Clinical Investigation·Andrea S RothmeierWolfram Ruf
Apr 16, 2010·Arteriosclerosis, Thrombosis, and Vascular Biology·Colin A KretzPeter L Gross
Jun 30, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·Randal J WestrickDaniel T Eitzman
Dec 23, 2009·Integrative Biology : Quantitative Biosciences From Nano to Macro·Welvitya KarunarathneDana M Spence
Mar 9, 2010·Expert Opinion on Therapeutic Patents·Hendra Gunosewoyo, Michael Kassiou
Feb 15, 2018·Frontiers in Pharmacology·Milka Koupenova, Katya Ravid
Apr 17, 2020·Platelets·Timothy J Stalker
May 20, 2014·Biomedit︠s︡inskai︠a︡ khimii︠a︡·V I ShaturnyĭM A Panteleev
Jul 11, 2020·Antibiotics·Samir Jawhara
Mar 25, 2021·Platelets·Cécile Oury, Odile Wéra
Apr 26, 2021·Drug Discovery Today·Lei ZhangZhe-Sheng Chen
Feb 3, 2009·Biochemistry·Frederick A OfosuSharon J Craven