Agonist and antagonist effects of diadenosine tetraphosphate, a platelet dense granule constituent, on platelet P2Y1, P2Y12 and P2X1 receptors.

Thrombosis Research
H ChangA L Frelinger

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

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Citations

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
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 28, 2016·Thrombosis and Haemostasis·Lydia R EngwenyuDominick J Angiolillo
Jan 17, 2017·Journal of Thrombosis and Haemostasis : JTH·A J GerritsA L Frelinger
May 3, 2014·Nature·Jin ZhangQiang Zhao
Apr 4, 2015·Molecular Pharmacology·Kenneth A JacobsonEvgeny Kiselev
Jun 22, 2021·Frontiers in Immunology·Xiang-Zhi FangYou Shang

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