Simonson M S, Osanai T, Dunn M J
Department of Medicine, Case Western Reserve University, School of Medicine, Cleveland, Ohio.
Clin Invest Med. 1991 Dec;14(6):499-507.
Isopeptides of the endothelin gene family, including sarafotoxin, caused a concentration-dependent increase in intracellular-free calcium (cytosolic calcium) in cultured human and rat glomerular mesangial cells. The calcium increments had two components, a spike increment resulting from mobilization of intracellular calcium and a sustained calcium increment as a result of endothelin activation of calcium influx. ET-dependent calcium influx occurred through dihydropyridine-insensitive calcium channels which were blocked by NiCl and allowed entry of Mn2+. In human mesangial cells, ET stimulated periodic oscillations of cytosolic Ca2+ that reflect synchronous signalling in localized populations. Calcium signalling evoked by the ET isopeptides showed cross-desensitization among the four ET-peptides tested. Although protein kinase C activation acutely reduced ET-induced calcium signalling, the desensitization by ET isopeptides was independent of protein kinase C. If ET was added to cells incubated with an inhibitor of the endoplasmic reticulum calcium ATPase, it became apparent that ET activated a calcium efflux pathway which reduced cytosolic calcium. These data, therefore, demonstrate that calcium signalling is a common response in both human and rat cultured mesangial cells incubated with different ET isopeptides.
内皮素基因家族的异肽，包括芋螺毒素，可使培养的人及大鼠肾小球系膜细胞内游离钙（胞质钙）浓度依赖性增加。钙增加有两个部分，一个是细胞内钙动员引起的峰值增加，另一个是内皮素激活钙内流导致的持续钙增加。内皮素依赖性钙内流通过对二氢吡啶不敏感的钙通道发生，该通道被氯化镍阻断并允许锰离子进入。在人系膜细胞中，内皮素刺激胞质钙的周期性振荡，这反映了局部群体中的同步信号传导。内皮素异肽诱发的钙信号在测试的四种内皮素肽之间表现出交叉脱敏。虽然蛋白激酶C激活可急性降低内皮素诱导的钙信号，但内皮素异肽引起的脱敏与蛋白激酶C无关。如果将内皮素添加到用内质网钙ATP酶抑制剂孵育的细胞中，就会明显发现内皮素激活了一条钙外流途径，从而降低了胞质钙。因此，这些数据表明，在用不同内皮素异肽孵育的人及大鼠培养系膜细胞中，钙信号是一种常见反应。
