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 cyclooxygenase inhibitor. These data suggest that ET-3 stimulates, in addition to EDRF (NO), the synthesis and release of prostacyclin.
Emori
T
T
Second Department of Internal Medicine, Tokyo Medical and Dental University, Japan.
Hirata
Y
Y
Marumo
F
F
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D016232:Endothelins / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D007213:Indomethacin / Q000494:pharmacology; D013268:Stimulation, Chemical
D016232:Endothelins; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D007213:Indomethacin