Abstract
Diadenosine 5',5'''-P(1),P(4)- tetraphosphate (Ap(4)A) is stored in platelet dense granules, but its effects on platelet function are not well understood. We examined the effects of Ap(4)A on platelet purinergic receptors P2Y(1), P2Y(12) and P2X(1). Flow cytometry was used to measure the effects of Ap(4)A in the presence or absence of ADP on: a) P2Y(12)-mediated decrease in intraplatelet phosphorylated vasodilator stimulated phosphoprotein (VASP), b) P2Y(1)-mediated increase in platelet cytosolic Ca(2+), and c) P2X(1)-mediated intraplatelet entry of extracellular Ca(2+). ADP-stimulated platelet shape change (P2Y(1)-mediated) and aggregation (P2Y(1)- and P2Y(12)-mediated) were measured optically. Ap(4)A inhibited 3 microM ADP-induced: a) platelet aggregation (IC(50) 9.8+/-2.8 microM), b) P2Y(1)-mediated shape change, c) P2Y(1)-mediated increase in platelet cytosolic Ca(2+) (IC(50) 40.8+/-12.3 microM), and d) P2Y(12)-mediated decrease in VASP phosphorylation (IC(50)>250 microM). In the absence of added ADP, Ap(4)A had agonist effects on platelet P2X(1) and P2Y(12), but not P2Y(1), receptors. Ap(4)A, a constituent of platelet dense granules, is a) an antagonist of platelet P2Y(1) and P2Y(12) receptors, where it inhibits the effect...Continue Reading
References
Jun 1, 1975·FEBS Letters·M J Harrison, R Brossmer
Mar 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·P C ZamecnikG M Blackburn
Mar 15, 1988·Thrombosis Research·S LouieP Zamecnik
Aug 30, 1983·Biochemical and Biophysical Research Communications·J Lüthje, A Ogilvie
May 1, 1996·British Journal of Pharmacology·J B SchachterT K Harden
Apr 15, 1997·Proceedings of the National Academy of Sciences of the United States of America·S W ChanP C Zamecnik
Dec 1, 1996·Journal of Autonomic Pharmacology·H SchlüterW Zidek
Jan 16, 1998·Prostaglandins, Leukotrienes, and Essential Fatty Acids·S O SageM P Mahaut-Smith
Jan 27, 1998·The Journal of Biological Chemistry·J JinS P Kunapuli
Apr 23, 1999·Cytometry·M do Céu MonteiroJ E O'Connor
Aug 6, 1999·Cardiovascular Research·N A FloresD J Sheridan
Feb 24, 2001·Journal of Hypertension·P HollahK H Rahn
Nov 17, 2001·European Journal of Pharmacology·K PatelF Marshall
Mar 22, 2003·The Journal of Pharmacology and Experimental Therapeutics·Aaron J MarcusRoberto Levi
Jun 9, 1962·Nature·G V BORN
Jun 10, 2004·Blood·Adam R HardyAlastair W Poole
Jun 19, 2004·Platelets·Martyn P Mahaut-SmithRichard J Evans
Jan 7, 2005·Journal of Thrombosis and Haemostasis : JTH·B AleilC Gachet
May 26, 2005·Blood·Gwen TolhurstMartyn P Mahaut-Smith
Oct 25, 2006·Journal of Thrombosis and Haemostasis : JTH·B N KahnerS P Kunapuli
Feb 26, 2008·Platelets·P ManolopoulosS Heptinstall
Oct 1, 1998·Drug Development Research·Yong-Chul KimKenneth A Jacobson
Citations
Apr 12, 2014·PloS One·Hung ChangAndrew L Frelinger
Apr 13, 2011·Purinergic Signalling·Martyn P Mahaut-SmithRichard J Evans
Apr 13, 2011·Purinergic Signalling·Kenneth A JacobsonStefano Costanzi
Mar 12, 2013·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Olivier MorelThierry Hannedouche
Nov 21, 2015·European Journal of Medicinal Chemistry·Ivan B YanachkovAndrew L Frelinger
Oct 23, 2012·Journal of Thrombosis and Haemostasis : JTH·H ChangA L Frelinger
Aug 12, 2015·Purinergic Signalling·Geoffrey Burnstock
Jul 8, 2015·Journal of Thrombosis and Haemostasis : JTH·M Cattaneo
Jul 22, 2015·Journal of Computer-aided Molecular Design·Silvia PaolettaKenneth A Jacobson
Sep 22, 2012·Blood·Ronald A AlbrightDemetrios T Braddock
Aug 8, 2013·PloS One·Vera JankowskiJoachim Jankowski
Aug 16, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Zoubir DjeradaHervé Millart
Oct 21, 2016·Purinergic Signalling·David ReigadaManuel Nieto-Díaz
Oct 28, 2016·Thrombosis and Haemostasis·Lydia R EngwenyuDominick J Angiolillo
Jan 17, 2017·Journal of Thrombosis and Haemostasis : JTH·A J GerritsA L Frelinger
Apr 30, 2014·European Journal of Immunology·Yan YangFang Zheng
May 3, 2014·Nature·Jin ZhangQiang Zhao
Apr 2, 2010·The Journal of Biological Chemistry·Stepan GambaryanUlrich Walter
Jan 9, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Thomas GremmelKarin Przyklenk
Mar 13, 2019·Journal of the American Heart Association·Francesco FranchiUNKNOWN PLATO Investigators
Apr 4, 2015·Molecular Pharmacology·Kenneth A JacobsonEvgeny Kiselev
Sep 23, 2020·The Protein Journal·Meriem AmezianiFatima Laraba-Djebari
Jun 22, 2021·Frontiers in Immunology·Xiang-Zhi FangYou Shang
Dec 15, 2020·Journal of Medicinal Chemistry·Yu LeiShaojie Wang
Aug 31, 2021·RSC Medicinal Chemistry·Zhichang ZhaoJuan Wang