The mechanisms of actions were investigated in cultured rat aortic vascular smooth muscle A-10 cells. The A-10 cells have a single class of high affinity binding sites for ET with an apparent Mr of 65,000-75,000 on SDS-PAGE. Stimulation of cells with ET induces mobilization of Ca2+ from both intra- and extracellular pools to produce a biphasic increase in cytoplasmic free Ca2+ concentration. A dihydropyridine Ca2+ channel antagonist does not inhibit the second plateau phase of the [Ca2+]i increase which is dependent on extracellular Ca2+. ET stimulates phospholipase C to produce inositol trisphosphate and 1,2-diacylglycerol vai a pertussis toxin-insensitive G protein. These results indicate that the receptor activation by ET is coupled to phospholipase C activation and Ca2+ channel gating in vascular smooth muscle cells.