Endothelin isopeptides evoke Ca2+ signaling and oscillations of cytosolic free [Ca2+] in human mesangial cells.
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.
Simonson
M S
MS
Department of Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH.
Osanai
T
T
Dunn
M J
MJ
D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects; D002478:Cells, Cultured; D004095:Dihydropyridines / Q000494:pharmacology; D016232:Endothelins / Q000502:physiology*; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D011493:Protein Kinase C / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D014757:Viper Venoms / Q000494:pharmacology
D015220:Calcium Channels; D004095:Dihydropyridines; D016232:Endothelins; D014757:Viper Venoms; C057354:sarafotoxins s6; C038806:1,4-dihydropyridine; D011493:Protein Kinase C; D002118:Calcium