CA-2+SIGNALING BY DISTINCT ENDOTHELIN PEPTIDES IN GLOMERULAR MESANGIAL CELLS

被引:72
作者
SIMONSON, MS
DUNN, MJ
机构
[1] CASE WESTERN RESERVE UNIV, UNIV HOSP CLEVELAND,SCH MED,DEPT MED,DIV NEPHROL, CLEVELAND, OH 44106 USA
[2] CASE WESTERN RESERVE UNIV, UNIV HOSP CLEVELAND,SCH MED,DEPT PHYSIOL & BIOPHYS, DIV NEPHROL, CLEVELAND, OH 44106 USA
关键词
D O I
10.1016/0014-4827(91)90169-U
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. © 1991.
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页码:148 / 156
页数:9
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