Effect of intracellular Ca 2+concentration on endothelin-1 secretion

The role of intracellular free Ca 2+concentration ([Ca 2+] iin cellular regulation of endothelin-(ET-1) secretion was investigated in cultured porcine aortic endothelial cells of first passage. Intracellular Ca 2+concentration were adjusted between 50 nM and 1 μM using EGTA and thapsigargin, respectively. ET-1 secretion was maximal at [Ca 2+] iof 190–470 nM, and reduced at low (50 and 110 nM) and high (470 nM) [Ca 2+] i. The Ca 2+ionophores A23187 and ionomycin (each 1 μM), both of which raise [Ca 2+] iabove 1 μM, 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 Ca 2+and that Ca 2+ionophores reduce ET-1 secretion due to the inhibitory effect of high [Ca 2+] i.