Simonson M S, Osanai T, Dunn M J
Department of Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH.
Biochim Biophys Acta. 1990 Oct 15;1055(1):63-8. doi: 10.1016/0167-4889(90)90091-q.
Isopeptides of the newly discovered peptide family, endothelins (ET), caused a concentration-dependent increase in intracellular free [Ca2+] ([Ca2+]i) in human glomerular mesangial cells. ET isopeptides and sarafotoxin S6b caused transient and sustained [Ca2+]i waveforms which resulted from mobilization of intracellular Ca2+ stores and from Ca2+ influx through a dihydropyridine-insensitive Ca2+ channel. Ca2+ signaling evoked by ET isopeptides underwent a marked adaptive, desensitization response. Although activation of protein kinase C attenuated ET-induced Ca2+ signaling, desensitization by ET isopeptides was independent of protein kinase C. High concentrations of ET-1 and ET-2 also caused oscillations of [Ca2+]i that partially depended on extracellular Ca2+. These results suggest that an increase in [Ca2+]i constitutes a common pathway of signal transduction for the ET peptide family.
新发现的肽家族——内皮素（ET）的异肽，可使人类肾小球系膜细胞内的细胞内游离钙离子浓度（[Ca2+]i）呈浓度依赖性增加。ET异肽和芋螺毒素S6b可引起瞬时和持续的[Ca2+]i波形，这是由细胞内钙库的动员以及通过对二氢吡啶不敏感的钙通道的钙内流所致。ET异肽引发的钙信号经历了显著的适应性脱敏反应。虽然蛋白激酶C的激活减弱了ET诱导的钙信号，但ET异肽引起的脱敏与蛋白激酶C无关。高浓度的ET-1和ET-2也会引起[Ca2+]i振荡，这部分依赖于细胞外钙。这些结果表明，[Ca2+]i的增加构成了ET肽家族信号转导的共同途径。
