Calcium-dependent activation of phospholipase C by mechanical distension in renin-expressing As4.1 cells.
Calcium-dependent activation of phospholipase C by mechanical distension in renin-expressing As4.1 cells.
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DOI：
10.1152/ajpendo.2000.279.4.e823
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发表时间：
2000-10
期刊：
影响因子：
--
通讯作者：
M. Ryan;K. Gross;G. Hajduczok
中科院分区：
文献类型：
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作者：
M. Ryan;K. Gross;G. Hajduczok
从肾脏产生和释放肾素的主要生理调节剂之一是血压。肾小球（JG）细胞主要位于通向肾小球的传入小动脉处，被认为是肾脏的压力感受器，并且以与压力（机械力）的变化成反比的关系调节它们分泌肾素的能力。JG细胞在细胞水平上感知和响应机械力变化的特征尚不清楚。通过使用一个表达肾素的克隆细胞系（As4.1）作为模型的JG细胞，这是本文的目的，以确定细胞的途径，被激活的机械扩张。Fura 2标记的As4.1细胞机械探针法观察细胞内钙离子浓度（[Ca（2+）]（i））的变化。As4.1细胞的机械扩张导致Ca（2+）内流到胞质溶胶，由牵张激活的离子通道介导，并依赖于细胞外Ca（2+）的存在。此外，周期性机械扩张提高了As4.1细胞中的总肌醇磷酸（IP）。这种反应也依赖于细胞外Ca（2+）的存在，并且加入磷脂酶C（PLC）拮抗剂U-73122显著减弱IP的增加。综上所述，这些发现表明PLC的钙依赖性激活以及随后IP和[Ca（2+）]（i）的增加是表达肾素的细胞响应于机械刺激的压力感知模式的潜在重要途径。
One of the major physiological regulators for the production and release of renin from the kidney is blood pressure. The juxtaglomerular (JG) cells, located primarily at the afferent arterioles leading to the glomerulus, are thought to be the baroreceptor of the kidney and adjust their ability to secrete renin in an inverse relationship to changes in pressure (mechanical force). The characteristics of JG cells that allow them to sense and respond to changes in mechanical force at the cellular level are not clear. By use of a renin-expressing clonal cell line (As4.1) as a model for JG cells, it was the purpose of this paper to identify cellular pathways that are activated by mechanical distension. Fura 2-labeled As4.1 cells were mechanically probed to observe changes of intracellular calcium concentration ([Ca(2+)](i)). Mechanical distension of As4.1 cells resulted in an influx of Ca(2+) to the cytosol, mediated by stretch-activated ion channels and dependent on the presence of extracellular Ca(2+). Furthermore, cyclic mechanical distension elevated total inositol phosphates (IP) in As4.1 cells. This response was also dependent on the presence of extracellular Ca(2+), and the addition of U-73122, a phospholipase C (PLC) antagonist, significantly attenuated the increase of IP. Taken together, these findings demonstrate the calcium-dependent activation of PLC and the subsequent increase of IP and [Ca(2+)](i) to be a potentially important pathway for the modality of pressure sensing by renin-expressing cells in response to mechanical stimulation.