Structure‐activity relationship in vasoconstrictor effects of sarafotoxins andendothelin‐1

Abstract

Sarafotoxins (SRTa, SRTb and SRTc) as well as endothelin‐1 (ET‐1) produced vasoconstrictions in rat thoracic aorta, rat isolated perfused mesentery and pithed rat in various of extents. The potency was ET‐1 > SRTb > SRTa > SRTc at lower doses, but SRTb > ET‐1 > SRTa > SRTc at higher doses. [Nitrophenylsulfenylated Trp 21 ]SRTb and SRTb(1‐19) caused no vasoconstriction. Either the reduction and carboxymethylation of Cys residues, the destruction of the intramolecular loop or the production of the non‐natural disulfide bond, eliminated the constrictor activity. These results indicate that Trp 21 and the intramolecular loop structure are essential, and Lys 9 and Tyr 13 may play some important roles for the vasoconstrictor activity of these peptides.