GENERATION OF CALCIUM OSCILLATIONS IN FIBROBLASTS BY POSITIVE FEEDBACK BETWEEN CALCIUM AND IP3
GENERATION OF CALCIUM OSCILLATIONS IN FIBROBLASTS BY POSITIVE FEEDBACK BETWEEN CALCIUM AND IP3
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DOI：
10.1126/science.1986413
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发表时间：
1991-01-04
期刊：
影响因子：
56.9
通讯作者：
TSIEN, RY
中科院分区：
文献类型：
--
作者：
HAROOTUNIAN, AT;KAO, JPY;TSIEN, RY
当参与肌醇磷脂信号通路的激动剂刺激时，多种不能兴奋的细胞产生胞浆钙离子浓度([Ca~(2+)]i)的重复性瞬时升高。关于钙离子是否抑制或刺激其自身从内库释放，以及肌醇1，4，5-三磷酸(IP3)和二酰甘油(DG)是否也经历与钙离子尖峰相关的振荡，目前关于振荡机制的理论存在分歧。在这项研究中，发现在有丝分裂原加去极化预刺激的REF52成纤维细胞中，钙离子可以刺激自身释放。然而，与肌肉和神经细胞中的钙释放不同，这种扩增对咖啡因或兰尼定不敏感，需要激素受体占位和功能上的IP3受体。[Ca~(2+)]i的波动伴随着IP3浓度的波动，但不需要功能蛋白激酶C。因此，一旦磷脂酶C被激素受体激活，这种细胞类型的主要反馈机制似乎是Ca~(2+)对该酶的刺激。
A wide variety of nonexcitable cells generate repetitive transient increases in cytosolic calcium ion concentration ([Ca2+]i) when stimulated with agonists that engage the phosphoinositide signalling pathway. Current theories regarding the mechanisms of oscillation disagree on whether Ca2+ inhibits or stimulates its own release from internal stores and whether inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DG) also undergo oscillations linked to the Ca2+ spikes. In this study, Ca2+ was found to stimulate its own release in REF52 fibroblasts primed by mitogens plus depolarization. However, unlike Ca2+ release in muscle and nerve cells, this amplification was insensitive to caffeine or ryanodine and required hormone receptor occupancy and functional IP3 receptors. Oscillations in [Ca2+]i were accompanied by oscillations in IP3 concentration but did not require functional protein kinase C. Therefore, the dominant feedback mechanism in this cell type appears to be Ca2+ stimulation of phospholipase C once this enzyme has been activated by hormone receptors.