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 Trp²¹]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 Trp²¹ and the intramolecular loop structure are essential, and Lys⁹ and Tyr¹³ may play some important roles for the vasoconstrictor activity of these peptides.