Peroxynitrite modulates receptor-activated Ca2+ signaling in vascular endothelial cells.
Peroxynitrite modulates receptor-activated Ca2+ signaling in vascular endothelial cells.
复制标题
过氧亚硝酸盐调节血管内皮细胞中受体激活的 Ca2 信号传导。
DOI：
10.1152/ajplung.1996.270.6.l954
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Elliott,SJ
中科院分区：
文献类型：
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作者：
Elliott,SJ
过氧亚硝酸盐（ONOO-）是由超氧阴离子（O2-）和NO形成的，我们以前曾报道过O2-不改变内皮细胞的Ca 2+信号。为了测试.NO是否改变Ca 2+信号传导，将细胞与.NO供体精胺NONOate孵育。精胺NONOate和S-亚硝基-N-乙酰青霉胺（SNAP）均不改变缓激肽刺激的Ca 2+信号。相比之下，3-吗啉苷酮亚胺（SIN-1）通过基本上同时释放O2-和NO产生ONOO-，显着抑制信号传导。最初，1 mM SIN-1的抑制作用对激动剂刺激的外部Ca 2+内流具有选择性。在稍后的时间点，SIN-1另外耗尽可释放的Ca 2+的内部储存。当细胞与SIN-1加超氧化物歧化酶共孵育时，Ca 2+信号传导与对照相同。SIN-1的非活性代谢产物SIN-1C对[Ca ~（2+）]i无影响。这项研究表明，外源性产生的ONOO-调节内皮细胞钙信号，表明ONOO-是血管调节的生物学相关性。
Peroxynitrite (ONOO-) is formed from superoxide (O2-) and .NO. We have previously reported that O2- does not alter endothelial cell Ca2+ signaling. To test whether .NO alters Ca2+ signaling, cells were incubated with the .NO donor, spermine NONOate. Neither spermine NONOate nor S-nitroso-N-acetyl penicillamine (SNAP) altered bradykinin-stimulated Ca2+ signaling. By contrast, 3-morpholinosydnonimine (SIN-1), which generates ONOO- by releasing O2- and .NO essentially in a simultaneous manner, significantly inhibited signaling. Initially, the inhibitory effect of 1 mM SIN-1 was selective toward agonist-stimulated influx of external Ca2+. At later time points, SIN-1 additionally depleted internal stores of releasable Ca2+. When cells were coincubated with SIN-1 plus superoxide dismutase, a technique designed to scavenge O2- and convert SIN-1 to purely an .NO-donor compound, Ca2+ signaling was identical to control. SIN-1C, the inactive metabolite of SIN-1, had no effect on [Ca2+]i. This study demonstrates that exogenously generated ONOO- modulates endothelial cell Ca2+ signaling, suggesting that ONOO- is of biological relevance to vasoregulation.