Effect of intracellular Ca2+ concentration on endothelin-1 secretion.
The role of intracellular free Ca2+ concentration ([Ca2+]i) in cellular regulation of endothelin-1 (ET-1) secretion was investigated in cultured porcine aortic endothelial cells of first passage. Intracellular Ca2+ concentrations were adjusted between 50 nM and 1 microM using EGTA and thapsigargin, respectively. ET-1 secretion was maximal at [Ca2+]i of 190-470 nM, and reduced at low (50 and 110 nM) and high (> 470 nM) [Ca2+]i. The Ca2+ ionophores A23187 and ionomycin (each 1 microM), both of which raise [Ca2+]i above 1 microM, also potently inhibited ET-1 secretion under basal and stimulated conditions. The A23187-induced reduction in ET-1 secretion was not affected by NG-nitro-L-arginine (0.1 mM). Our results provide evidence that basal ET-1 secretion is regulated by Ca2+ and that Ca2+ ionophores reduce ET-1 secretion due to the inhibitory effect of high [Ca2+]i.
Brunner
F
F
Institut für Pharmakologie und Toxikologie, Karl-Franzens-Universität Graz, Austria.
Stessel
H
H
Simecek
S
S
Graier
W
W
Kukovetz
W R
WR
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D016232:Endothelins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D016232:Endothelins; D000001:Calcimycin; D015759:Ionomycin; D007770:L-Lactate Dehydrogenase; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium