Specific receptors for endothelin‐3 in cultured bovine endothelial cells and its cellular mechanism of action

Abstract

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 ([Ca⁻²]) 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.