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dc.contributor.authorChang, Hung
dc.contributor.authorYanachkov, Ivan B.
dc.contributor.authorMichelson, Alan D.
dc.contributor.authorLi, YouFu
dc.contributor.authorBarnard, Marc R.
dc.contributor.authorWright, George E.
dc.contributor.authorFrelinger, Andrew L. III
dc.date2022-08-11T08:10:10.000
dc.date.accessioned2022-08-23T16:58:14Z
dc.date.available2022-08-23T16:58:14Z
dc.date.issued2009-12-01
dc.date.submitted2012-04-25
dc.identifier.citationThromb Res. 2010 Feb;125(2):159-65. Epub 2009 Nov 27. <a href="http://dx.doi.org/10.1016/j.thromres.2009.11.006">Link to article on publisher's website</a>
dc.identifier.issn0049-3848 (Linking)
dc.identifier.doi10.1016/j.thromres.2009.11.006
dc.identifier.pmid19945153
dc.identifier.urihttp://hdl.handle.net/20.500.14038/43324
dc.description.abstractINTRODUCTION: 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. METHODS AND RESULTS: 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. CONCLUSION: 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 effects of ADP, and b) an agonist of platelet P2X(1) and P2Y(12) receptors.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=19945153&dopt=Abstract">Link to article in PubMed</a>
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2826549/pdf/nihms158782.pdf
dc.subjectBlood Platelets
dc.subjectCytoplasmic Granules
dc.subjectDinucleoside Phosphates
dc.subjectDose-Response Relationship, Drug
dc.subjectHumans
dc.subject*Purinergic P2 Receptor Agonists
dc.subject*Purinergic P2 Receptor Antagonists
dc.subjectReceptors, Purinergic P2X
dc.subjectReceptors, Purinergic P2Y1
dc.subjectReceptors, Purinergic P2Y12
dc.subjectHematology
dc.subjectOncology
dc.subjectPediatrics
dc.titleAgonist and antagonist effects of diadenosine tetraphosphate, a platelet dense granule constituent, on platelet P2Y1, P2Y12 and P2X1 receptors
dc.typeJournal Article
dc.source.journaltitleThrombosis research
dc.source.volume125
dc.source.issue2
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/peds_hematology/127
dc.identifier.contextkey2796617
html.description.abstract<p>INTRODUCTION: 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.</p> <p>METHODS AND RESULTS: 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.</p> <p>CONCLUSION: 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 effects of ADP, and b) an agonist of platelet P2X(1) and P2Y(12) receptors.</p>
dc.identifier.submissionpathpeds_hematology/127
dc.contributor.departmentDepartment of Pediatrics
dc.source.pages159-65


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