ENDOTHELIN-3 STIMULATES PROSTACYCLIN PRODUCTION IN CULTURED BOVINE ENDOTHELIAL-CELLS

Among three endothelin (ET) isopeptides, ET-3 shows the most potent initial depressor response through endothelium-dependent mechanism. We have recently reported that ET-3 induces receptor-mediated phosphoinositide breakdown, which increases the intracellular Ca2+ concentration ([Ca2+]i) and stimulates synthesis of endothelium-derived relaxing factor (EDRF), or nitric oxide (NO), in endothelial cells (ECs). We examined whether ET-3 has any effect on synthesis of prostacyclin, a potent vasodilator prostanoid in bovine ECs. ET-3 dose-dependently (10(-10)-10(-8) M) stimulated the formation of 6-keto-prostaglandin F1-alpha, a stable metabolite of prostacyclin, in culture media of ECs, whose stimulatory effect was inhibited by indomethacin, a cyclo-oxgenase inhibitor. These data suggest that ET-3 stimulates, in addition to EDRF (NO), the synthesis and release of prostacyclin.