Regulation of phosphoinositide hydrolysis and cytosolic free calcium induced by endothelin in human glomerular epithelial cells.
The regulation of the inositide signalling pathway and [Ca2+]i by endothelin (ET) peptides was investigated in human glomerular epithelial cells in culture. Endothelin-1 and -2 induced an accumulation of inositol phosphates in a time- and dose-dependent manner. The baseline of [Ca2+]i in glomerular epithelial cells was 109 +/- 2.8 nmol/l, n = 60. Endothelin-1 (ED50: approx. 3 x 10(-9) mol/l) caused a rapid and transient rise in [Ca2+]i as detected by fura-2 microfluorimetry studies. The endothelin-1-induced inositol phosphate accumulation was inhibited by the selective ETA receptor antagonist BQ123. Endothelin-3 and BQ3020, a selective ETB receptor agonist, showed no effect. The results suggest an ETA-mediated pathway. This study demonstrates an ETA-mediated transmembrane signalling via phospholipase C with consecutive elevation of inositol phosphates and intracellular calcium. Since endothelin peptides contribute to both normal renal function and renal dysfunction, this study adds further knowledge on glomerular cell regulation.
Medizinische Universitätsklinik, Abteilung Innere Medizin IV, Freiburg, Germany.
M
M
Späth
H
H
Pavenstädt
C
C
Müller
J
J
Petersen
C
C
Wanner
P
P
Schollmeyer
D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003592:Cytophotometry; D016232:Endothelins / Q000494:pharmacology / Q000502:physiology*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis / Q000187:drug effects; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D016232:Endothelins; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D010716:Phosphatidylinositols; D010566:Virulence Factors, Bordetella; C075771:BQ 3020; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D002118:Calcium