Simonson M S, Dunn M J
Department of Medicine, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106.
Exp Cell Res. 1991 Jan;192(1):148-56. doi: 10.1016/0014-4827(91)90169-u.
Ca2+ signaling by peptides of the endothelin (ET) gene family was studied in cultured glomerular mesangial cells. In addition to the increase in cytosolic free [Ca2+] ([Ca2+]i) previously described for ET-1, we also observed that ET-2, ET-3, and sarafotoxin S6b generate similar [Ca2+]i waveforms but with dissimilar potencies and kinetics. The prepro form of ET-1 was inactive, suggesting that mature ET peptides are constrained in an inactive conformation within the preproET species. ET isopeptides caused both release of Ca2+ from intracellular stores and Ca2+ influx via a voltage- and dihydropyridine-insensitive pathway. ET-mediated Ca2+ influx was independent of the increase in [Ca2+]i. Activation of protein kinase C inhibited ET-induced Ca2+ signaling, whereas addition of ET to protein kinase C-depleted cells resulted in enhanced [Ca2+]i waveforms. Mesangial cells also demonstrated a marked adaptive desensitization response to ET. These data demonstrate that Ca2+ signaling is a common response to different ET peptides in glomerular mesangial cells and that activation of protein kinase C down-regulates these Ca2+ signals.
我们在培养的肾小球系膜细胞中研究了内皮素（ET）基因家族肽段的钙离子信号传导。除了先前描述的ET-1可使胞质游离钙离子浓度（[Ca2+]i）升高外，我们还观察到ET-2、ET-3和肉瘤毒素S6b可产生相似的[Ca2+]i波形，但效力和动力学不同。ET-1的前体形式无活性，这表明成熟的ET肽段在前体ET分子中处于无活性构象。ET同工肽可引起细胞内钙库释放Ca2+以及通过一条对电压和二氢吡啶不敏感的途径使Ca2+内流。ET介导的Ca2+内流与[Ca2+]i的升高无关。蛋白激酶C的激活可抑制ET诱导的钙离子信号传导，而将ET添加到蛋白激酶C缺失的细胞中则会导致[Ca2+]i波形增强。系膜细胞对ET还表现出明显的适应性脱敏反应。这些数据表明，钙离子信号传导是肾小球系膜细胞对不同ET肽段的常见反应，并且蛋白激酶C的激活会下调这些钙离子信号。
