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Adrenoceptor α2A signalling countervails the taming effects of synchronous cyclic nucleotide-elevation on thrombin-induced human platelet activation and aggregation
Örebro University, School of Medical Sciences. Cardiovascular Research Centre (CVRC).ORCID iD: 0000-0003-2519-203x
Örebro University, School of Medical Sciences. Cardiovascular Research Centre (CVRC).ORCID iD: 0000-0003-4253-3369
Örebro University, School of Medical Sciences. Cardiovascular Research Centre (CVRC).ORCID iD: 0000-0002-5025-9454
Örebro University, School of Medical Sciences. Cardiovascular Research Centre (CVRC).ORCID iD: 0000-0002-2732-158x
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2019 (English)In: Cellular Signalling, ISSN 0898-6568, E-ISSN 1873-3913, Vol. 59, p. 96-109Article in journal (Refereed) Published
Abstract [en]

The healthy vascular endothelium constantly releases autacoids which cause an increase of intracellular cyclic nucleotides to tame platelets from inappropriate activation. Elevating cGMP and cAMP, in line with previous reports, cooperated in the inhibition of isolated human platelet intracellular calcium-mobilization, dense granules secretion, and aggregation provoked by thrombin. Further, platelet alpha granules secretion and, most relevant, integrin αIIaβ3 activation in response to thrombin are shown to be prominently affected by the combined elevation of cGMP and cAMP. Since stress-related sympathetic nervous activity is associated with an increase in thrombotic events, we investigated the impact of epinephrine in this setting. We found that the assessed signalling events and functional consequences were to various extents restored by epinephrine, resulting in full and sustained aggregation of isolated platelets. The restoring effects of epinephrine were abolished by either interfering with intracellular calcium-elevation or with PI3-K signalling. Finally, we show that in our experimental setting epinephrine likewise reconstitutes platelet aggregation in heparinized whole blood, which may indicate that this mechanism could also apply in vivo.

Place, publisher, year, edition, pages
Elsevier, 2019. Vol. 59, p. 96-109
Keywords [en]
Cyclic nucleotide, Epinephrine, Human platelets, Nitric oxide, Prostacyclin, α(2A) adrenoceptor
National Category
Physiology and Anatomy Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:oru:diva-73421DOI: 10.1016/j.cellsig.2019.03.019ISI: 000468251000010PubMedID: 30926386Scopus ID: 2-s2.0-85063486315OAI: oai:DiVA.org:oru-73421DiVA, id: diva2:1302447
Funder
AFA Insurance, 130275Knowledge Foundation, 20150240Available from: 2019-04-04 Created: 2019-04-04 Last updated: 2025-02-10Bibliographically approved

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Fälker, KnutLjungberg, LizaKardeby, CarolineLindkvist, MadeleneSirsjö, AllanGrenegård, Magnus

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