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• W4313563248 endingPage "100004" @default.
• W4313563248 startingPage "100004" @default.
• W4313563248 abstract "BackgroundBlood platelet Ca2+ stores are regulated by 2 Ca2+-ATPases (SERCA2b and SERCA3). On thrombin stimulation, nicotinic acid adenosine dinucleotide phosphate mobilizes SERCA3-dependent stores, inducing early adenosine 5‘-diphosphate (ADP) secretion, potentiating later SERCA2b-dependent secretion.ObjectivesThe aim of this study was to identify which ADP P2 purinergic receptor (P2Y1 and/or P2Y12) is(are) involved in the amplification of platelet secretion dependent on the SERCA3-dependent Ca2+ mobilization pathway (SERCA3 stores mobilization) as triggered by low concentration of thrombin.MethodsThe study used the pharmacologic antagonists MRS2719 and AR-C69931MX, of the P2Y1 and P2Y12, respectively, as well as Serca3-/- mice and mice exhibiting platelet lineage-specific inactivation of the P2Y1 or P2Y12 genes.ResultsWe found that in mouse platelets, pharmacological blockade or gene inactivation of P2Y12 but not of P2Y1 led to a marked inhibition of ADP secretion after platelet stimulation with low concentration of thrombin. Likewise, in human platelets, pharmacological inhibition of P2Y12 but not of P2Y1 alters amplification of thrombin-elicited secretion through SERCA2b stores mobilization. Finally, we show that early SERCA3 stores secretion of ADP is a dense granule secretion, based on parallel adenosine triphosphate and serotonin early secretion. Furthermore, early secretion involves a single granule, based on the amount of adenosine triphosphate released.ConclusionAltogether, these results show that at low concentrations of thrombin, SERCA3- and SERCA2b-dependent Ca2+ mobilization pathways cross-talk via ADP and activation of the P2Y12, and not the P2Y1 ADP receptor. The relevance in hemostasis of the coupling of the SERCA3 and the SERCA2b pathways is reviewed." @default.
• W4313563248 created "2023-01-06" @default.
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• W4313563248 date "2023-01-01" @default.
• W4313563248 modified "2023-10-03" @default.
• W4313563248 title "ADP receptor P2Y12 is the capstone of the cross-talk between Ca2+ mobilization pathways dependent on Ca2+ ATPases sarcoplasmic/endoplasmic reticulum type 3 and type 2b in platelets" @default.
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• W4313563248 doi "https://doi.org/10.1016/j.rpth.2022.100004" @default.
• W4313563248 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36970741" @default.
• W4313563248 hasPublicationYear "2023" @default.
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