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Flavonoids inhibit the platelet TxA2 signalling pathway and antagonize TxA2 receptors (TP) in platelets and smooth muscle cells

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dc.contributor.authorGuerrero López, José Antonio
dc.contributor.authorNavarro-Nuñez, Leyre
dc.contributor.authorLozano Almela, María Luisa
dc.contributor.authorMartínez, Constantino
dc.contributor.authorVicente García, Vicente
dc.contributor.authorGibbins, Jonathan M.
dc.contributor.authorRivera Pozo, José
dc.contributor.departmentMedicina Interna
dc.contributor.departmentMedicina
dc.contributor.otherFacultad de Medicina
dc.date.accessioned2026-01-28T09:04:47Z
dc.date.available2026-01-28T09:04:47Z
dc.date.copyright© 2007 The Authors © 2007 Blackwell Publishing Ltd
dc.date.issued2007-04-10
dc.description.abstractAims: Flavonoids may affect platelet function by several mechanisms, including antagonism of TxA2 receptors (TP). These TP are present in many tissues and modulate different signalling cascades. We explored whether flavonoids affect platelet TP signalling, and if they bind to TP expressed in other cell types. Methods: Platelets were treated with flavonoids, or other selected inhibitors, and then stimulated with U46619. Similar assays were performed in aspirinized platelets activated with thrombin. Effects on calcium release were analysed by fluorometry and changes in whole protein tyrosine phosphorylation and activation of ERK 1/2 by Western blot analysis. The binding of flavonoids to TP in platelets, human myometrium and TPaand TPb-transfected HEK 293T cells was explored using binding assays and the TP antagonist 3H-SQ29548. Results: Apigenin, genistein, luteolin and quercetin impaired U46619-induced calcium mobilization in a concentration-dependent manner (IC50 10–30 mm). These flavonoids caused a significant impairment of U46619-induced platelet tyrosine phosphorylation and of ERK 1/2 activation. By contrast, in aspirin-treated platelets all these flavonoids, except quercetin, displayed minor effects on thrombin-induced calcium mobilization, ERK 1/2 and total tyrosine phosphorylation. Finally, apigenin, genistein and luteolin inhibited by >50% 3H-SQ29548 binding to different cell types. Conclusions: These data further suggest that flavonoids may inhibit platelet function by binding to TP and by subsequent abrogation of downstream signalling. Binding of these compounds to TP occurs in human myometrium and in TP-transfected HEK 293T cells and suggests that antagonism of TP might mediate the effects of flavonoids in different tissues.
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dc.format.extent12
dc.identifier.citationBritish Journal of Clinical Pharmacology, 64: 133-144
dc.identifier.doihttps://doi.org/10.1111/j.1365-2125.2007.02881.x
dc.identifier.eissn1365-2125
dc.identifier.issn0306-5251
dc.identifier.urihttp://hdl.handle.net/10201/195749
dc.languageeng
dc.publisherWiley, British Pharmacological Society
dc.relationThis study was supported in part by a research grant from the Ministerio de Educación, Ciencia y Tecnología. (SAF 2004-07535). J.A.G. is a postdoctoral fellow of Ministerio de Educación y Ciencia (EX-2006-0429). L.N-N. is a fellow of Ministerio de Educación y Ciencia (BES-2005-7496). C.M. is a Ramón y Cajal investigator from the University of Murcia.
dc.rightsAttribution-NonCommercial-NoDerivates 4.0 International
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectFlavonoid
dc.subjectHEK 293T Cells
dc.subjectPlatelets
dc.subjectSmooth muscle cells
dc.subjectTP signalling
dc.subject.odsObjetivo 3: Salud
dc.titleFlavonoids inhibit the platelet TxA2 signalling pathway and antagonize TxA2 receptors (TP) in platelets and smooth muscle cells
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/acceptedVersión
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