Regulation of phosphoinositide hydrolysis and cytosolic free calcium induced by endothelin in human glomerular epitheial cells

The regulation of the inositide signalling pathway and [Ca²⁺]_iby endothelin (ET) peptides was investigated in human glomerularepithelial cells in culture. Endothelin-1 and -2 induced anaccumulation of inositol phosphates in a time- and dose-dependentmanner. The baseline of [Ca²⁺]_i, in glomerular epithelial cellswas 109±2.8 nmol/l, n=60. Endothelin-l (ED₅₀: approx.3x10 mol/l) caused a rapid and transient rise in [²⁺]_i as detectedby fura-2 microfluorimetry studies. The endothelin-l-inducedinositol phosphate accumulation was inhibited by the selectiveET_A recep tor antagonist BQ123. Endothelin-3 and BQ3020, a selectiveET_B receptor agonist, showed no effect. The results suggestan ETA-mediated pathway. This study demonstrates an ET_A-mediatedtransmembrane signalling via phospholipase C with consecutiveelevation of inositol phosphates and intracellular calcium.Since endothelin peptides contribute to both normal renal functionand renal dysfunction, this study adds further knowledge onglomerular cell regulation.