Endothelin isopeptides evoke Ca 2+ signaling and oscillations of cytosolic free [Ca 2+] in human mesangial cells

Abstract

Isopeptides of the newly discovered peptide family, endothelins (ET), caused a concentration-dependent increase in intracellular free [Ca 2+] ([Ca 2+] i) in human glomerular mesangial cells. ET isopeptides and sarafotoxin S6b caused transient and sustained [Ca 2+] i waveforms which resulted from mobilization of intracellular Ca 2+ stores and from Ca 2+ influx through a dihydropyridine-insensitive Ca 2+ channel. Ca 2+ signaling evoked by ET isopeptides underwent a marked adaptive, desensitization response. Although activation of protein kinase C attenuated ET-induced Ca 2+ signaling, desensitization by ET isopeptides was independent of protein kinase C. High concentrations of ET-1 and ET-2 also caused oscillations of [Ca 2+] i that partially depended on extracellular Ca 2+. These results suggest that an increase in [Ca 2+] i constitutes a common pathway of signal transduction for the ET peptide family.