SHEAR STRESS-INDUCED [CA2+](I) TRANSIENTS AND OSCILLATIONS IN MOUSE FIBROBLASTS ARE MEDIATED BY ENDOGENOUSLY RELEASED ATP
SHEAR STRESS-INDUCED [CA2+](I) TRANSIENTS AND OSCILLATIONS IN MOUSE FIBROBLASTS ARE MEDIATED BY ENDOGENOUSLY RELEASED ATP
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DOI：
10.1074/jbc.270.9.4451
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发表时间：
1995-03-03
影响因子：
4.8
通讯作者：
MELDOLESI, J
中科院分区：
文献类型：
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作者：
GRIERSON, JP;MELDOLESI, J
ATP、U-73122、腺苷三磷酸双磷酸酶和盐水剪切应力对 [Ca2+](i) 稳态的影响在加载 fura-2 的小鼠成纤维细胞 (L929)（悬浮液和铺在玻璃上）中进行了研究。内部 Ca2+ 的释放是由 ATP 诱导的，通过药理学上鉴定为 P-2U 型的受体，在单细胞中，引起低浓度的 ATP [Ca2+](i) 振荡，这些事件可被假定的磷脂酶 C 抑制剂 U-73122（但不能被无活性类似物 U-73343）和 ATP/ADPase、腺苷三磷酸双磷酸酶阻断。此外，这两种药物均可减少未刺激细胞的 [Ca2+](i)，特别是在搅拌后，并阻断自发产生的 [Ca2+](i) 振荡，这表明 ATP 受体已经处于激活状态，与外源刺激无关。此外，还发现细胞的搅拌与肌醇磷酸盐的稳定积累相关，也可被腺苷三磷酸双磷酸酶阻断，并且 [Ca2+](i) 动员可以通过单细胞中的盐水诱导。向无 Ca2+ 环境的转变也引发了 [Ca2+](i) 振荡，最有可能是通过 ATP(4-) 浓度的增加。这一证据表明，L 成纤维细胞响应流体剪切应力而释放内源 ATP，这导致磷酸肌醇信号系统的自分泌、强直性上调，以及随之而来的 Ca2+ 稳态改变。到目前为止，这种对剪切应力的反应被认为是内皮细胞所独有的。
The effects of ATP, U-73122, apyrase, and saline shear stress on [Ca2+](i) homeostasis were studied in fura-2 loaded, mouse fibroblast cells (L929), both in suspension and plated on glass, Release of internal Ca2+ was induced by ATP, via a receptor identified pharmacologically as a P-2U type, In single cells, low concentrations of ATP evoked [Ca2+](i) oscillations, These events were blocked by the putative phospholipase C inhibitor, U-73122 (but not by the inactive analog U-73343) and by the ATP/ADPase, apyrase, In addition, both these agents reduced the [Ca2+](i) of unstimulated cells, especially after stirring, and blocked spontaneously occurring [Ca2+](i) oscillations, which suggested an already activated state of the ATP receptor, independent from exogenous stimulations, Moreover, it was found that stirring of the cells was correlated with a steady accumulation of inositol phosphates, also blockable by apyrase, and that [Ca2+](i) mobilization could be induced by puffs of saline in single cells, The transition to a Ca2+-free environment also provoked [Ca2+](i) oscillations, most likely via the increase in ATP(4-) concentration, This evidence suggests that endogenous ATP is released from L fibroblasts in response to fluid shear stress, and this results in an autocrine, tonic up-regulation of the phosphoinositide signaling system and an ensuing alteration in Ca2+ homeostasis, Up until now, such a response to shear stress was believed to be unique to endothelial cells.