Specific receptors for endothelin-3 in cultured bovine endothelial cells and its cellular mechanism of action.
Among three endothelin (ET) isopeptides, ET-3 shows the most potent initial depressor response through the endothelium-dependent mechanism. We studied the presence of specific binding sites for ET-3 in cultured bovine endothelial cells (EC) and its cellular mechanism of action. Binding studies revealed the presence of two distinct subclasses of ET-3 receptors with high and low affinities. ET-3 dose-dependently (10(-10)-10(-7) M) increased both intracellular Ca2+ levels ([Ca2+]i) and inositol trisphosphate (IP3) formation. The ET-3-induced increase in [Ca2+]i was not affected by either removal of extracellular Ca2+ or Ca2(+)-channel blockers. These data suggest that ET-3 induces phosphoinositide breakdown and increase in [Ca2+]i in ECs, possibly resulting from intracellular Ca2+ mobilization, thereby leading to vasodilatation.
Emori
T
T
Second Department of Internal Medicine, Tokyo Medical and Dental University, Japan.
Hirata
Y
Y
Marumo
F
F
D000818:Animals; D001572:Benzofurans; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D016232:Endothelins; D004730:Endothelium, Vascular / Q000378:metabolism*; D005456:Fluorescent Dyes; D016257:Fura-2 / Q000031:analogs & derivatives*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D010455:Peptides / Q000378:metabolism* / Q000502:physiology; D011956:Receptors, Cell Surface / Q000032:analysis*; D017466:Receptors, Endothelin
D001572:Benzofurans; D016232:Endothelins; D005456:Fluorescent Dyes; D010455:Peptides; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; C049925:fura-2-am; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium; D016257:Fura-2