Structure-activity relationship in vasoconstrictor effects of sarafotoxins and endothelin-1.
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 greater than SRTb greater than SRTa greater than SRTc at lower doses, but SRTb greater than ET-1 greater than SRTa greater than 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.
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
K
K
Kitazumi
T
T
Shiba
K
K
Nishiki
Y
Y
Furukawa
C
C
Takasaki
K
K
Tasaka
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016232:Endothelins; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents; D014757:Viper Venoms / Q000494:pharmacology*
D016232:Endothelins; D010455:Peptides; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6