Ca2+ signaling by distinct endothelin peptides in glomerular mesangial cells.
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.
Simonson
M S
MS
Department of Medicine, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106.
Dunn
M J
MJ
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D004095:Dihydropyridines / Q000494:pharmacology; D015536:Down-Regulation; D016232:Endothelins / Q000502:physiology*; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D010455:Peptides / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D011498:Protein Precursors / Q000378:metabolism / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014757:Viper Venoms / Q000494:pharmacology
D015220:Calcium Channels; D004095:Dihydropyridines; D016232:Endothelins; D010455:Peptides; D011498:Protein Precursors; D014757:Viper Venoms; C057354:sarafotoxins s6; C038806:1,4-dihydropyridine; D011493:Protein Kinase C; D002118:Calcium