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• W1993695315 abstract "In this study the effects of nitric oxide (NO) donors on intracellular free calcium ([Ca2+]i) in human platelets was examined. Inhibition of guanylyl cyclase (GC) with either methylene blue or ODQ slightly inhibited the ability of submaximal concentrations of thrombin to increase [Ca2+]i which suggests that a small portion of the thrombin mediated increase in [Ca2+]i was due to an increase in NO and subsequent increase in cGMP and activation of cGMP dependent protein kinase (cGPK). Thrombin predominantly increases [Ca2+]i by stimulating store-operated Ca2+ entry (SOCE). The NO donor GEA3162 was previously shown to stimulate SOCE in some cells. In platelets GEA3162 had no effect to increase [Ca2+]i however it inhibited the ability of thrombin to increase [Ca2+]i and this effect was reversed by ODQ. The addition of low concentrations (2.0 – 20 nM) of the NO donor sodium nitroprusside (SNP) slightly potentiated the ability of thrombin to increase [Ca2+]i whereas higher concentrations (>200 nM) of SNP inhibited thrombin induced increases in [Ca2+]i. Both of these effects of SNP were reversed by ODQ which implies that they were both mediated by cGPK. Ba2+ influx was stimulated by low concentrations (2.0 nM) of SNP and inhibited by high concentrations (>200 nM) of SNP and both effects were inhibited by ODQ. Previous studies showed that Ba2+ influx was blocked by the SOCE inhibitors 2-aminoethoxydipheny borate and diethylstilbestrol. It was concluded that low levels of SNP can stimulate SOCE in platelets and this effect may account for the increased aggregation and secretion previously observed with low concentrations of NO donors. Of the proteins known to be involved in SOCE (e.g. stromal interaction molecule 1 (Stim1), Stim2 and Orai1) only Stim2 has cGPK phosphorylation sites. The possibility that Stim2 phosphorylation regulates SOCE in platelets is discussed." @default.
• W1993695315 created "2016-06-24" @default.
• W1993695315 creator A5050452260 @default.
• W1993695315 date "2011-01-01" @default.
• W1993695315 modified "2023-10-18" @default.
• W1993695315 title "Biphasic effects of nitric oxide on calcium influx in human platelets" @default.
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• W1993695315 doi "https://doi.org/10.1016/j.thromres.2010.10.002" @default.
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