Interaction of synthetic sarafotoxin with rat vascular endothelin receptors

Abstract

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 Ca 2+ concentration ([Ca 2+] i) were studied in cultured rat vascular smooth muscle cells. Binding studies revealed that [Cys 1–15, Cys 3–11] 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 [Cys 1–11, Cys 3–15]STX in inhibiting the binding. [Cys 1–15, Cys 3–11]STX had a less potent effect on increasing [Ca 2+] i than ET, whereas [Cys 1–11, Cys 3–15]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 [Ca 2+] i response.