English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/124438
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:
DC FieldValueLanguage
dc.contributor.advisorVASP-
dc.contributor.authorNygaard, Gyrid-
dc.contributor.authorHerfindal, Lars-
dc.contributor.authorKopperud, Reidun-
dc.contributor.authorAragay, Anna M.-
dc.contributor.authorHolmsen, Holm-
dc.contributor.authorDoskeland, Stein Ove-
dc.contributor.authorKleppe, Rune-
dc.contributor.authorSelheim, Frode-
dc.date.accessioned2015-11-04T11:16:35Z-
dc.date.available2015-11-04T11:16:35Z-
dc.date.issued2014-07-04-
dc.identifierdoi: 10.1016/j.bbrc.2014.05.032-
dc.identifierissn: 1090-2104-
dc.identifier.citationBiochemical and Biophysical Research Communications 449(3): 357-363 (2014)-
dc.identifier.urihttp://hdl.handle.net/10261/124438-
dc.description.abstractIn platelets, nitric oxide (NO) activates cGMP/PKG signalling, whereas prostaglandins and adenosine signal through cAMP/PKA. Cyclic nucleotide signalling has been considered to play an inhibitory role in platelets. However, an early stimulatory effect of NO and cGMP-PKG signalling in low dose agonist-induced platelet activation have recently been suggested. Here, we investigated whether different experimental conditions could explain some of the discrepancy reported for platelet cGMP-PKG-signalling. We treated gel-filtered human platelets with cGMP and cAMP analogues, and used flow cytometric assays to detect low dose thrombin-induced formation of small platelet aggregates, single platelet disappearance (SPD), platelet-derived microparticles (PMP) and thrombin receptor agonist peptide (TRAP)-induced P-selectin expression. All four agonist-induced platelet activation phases were blocked when platelets were costimulated with the PKG activators 8-Br-PET-cGMP or 8-pCPT-cGMP and low-doses of thrombin or TRAP. However, extended incubation with 8-Br-PET-cGMP decreased its inhibition of TRAP-induced P-selectin expression in a time-dependent manner. This effect did not involve desensitisation of PKG or PKA activity, measured as site-specific VASP phosphorylation. Moreover, PKG activators in combination with the PKA activator Sp-5,6-DCL-cBIMPS revealed additive inhibitory effect on TRAP-induced P-selectin expression. Taken together, we found no evidence for a stimulatory role of cGMP/PKG in platelets activation and conclude rather that cGMP/PKG signalling has an important inhibitory function in human platelet activation. © 2014 Elsevier Inc. All rights reserved.-
dc.description.sponsorshipThis study was supported by the Norwegian National Health Association and the Western Norway Regional Health Authority.-
dc.publisherAcademic Press-
dc.rightsclosedAccess-
dc.subjectcAMP-
dc.subjectcGMP-
dc.subjectcGMP-analogues-
dc.subjectPKG-
dc.subjectPlatelets-
dc.titleTime-dependent inhibitory effects of cGMP-analogues on thrombin-induced platelet-derived microparticles formation, platelet aggregation, and P-selectin expression-
dc.typeartículo-
dc.identifier.doi10.1016/j.bbrc.2014.05.032-
dc.relation.publisherversionhttp://dx.doi.org/10.1016/j.bbrc.2014.05.032-
dc.date.updated2015-11-04T11:16:35Z-
dc.description.versionPeer Reviewed-
dc.language.rfc3066eng-
dc.contributor.funderWestern Norway Regional Health Authority-
dc.contributor.funderNorwegian National Health Association-
dc.relation.csic-
Appears in Collections:(IBMB) Artículos
Files in This Item:
File Description SizeFormat 
accesoRestringido.pdf15,38 kBAdobe PDFThumbnail
View/Open
Show simple item record
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.