Interaction of synthetic sarafotoxin with rat vascular endothelin receptors

The effects of synthetic analogs of sarafotoxin (STX) S6b, a snake venom peptide with a high sequence homology to the endothelium-derived vasoconstrictor endothelin (ET), on ET receptor binding activity and cytosolic free Ca2+ concentration ( Ca2+]i) were studied in cultured rat vascular smooth muscle cells. Binding studies revealed that Cys1-15, Cys3-11] STX competed with 125I-ET for the binding to its vascular receptors with lower affinity than that of ET, but was far more effective than Cys1-11, Cys3-15]STX in inhibiting the binding. Cys1-15, Cys3-11]STX had a less potent effect on increasing Ca2+]i than ET, whereas Cys1-11, Cys3-15]STX was inactive. These data suggest that there may exist heterogenous subpopulations of the vascular ET/STX receptors, and that the proper double cyclic structure of STX is essential for interacting with its putative receptors to induce the Ca2+]i response.