Kitazumi K, Shiba T, Nishiki K, Furukawa Y, Takasaki C, Tasaka K
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Biochem Pharmacol. 1990 Oct 15;40(8):1843-7. doi: 10.1016/0006-2952(90)90365-r.
Sarafotoxins (SRTa, SRTb and SRTc) and ET-1 produced a potent vasodilator effect in spontaneously hypertensive rats in vivo and in rat isolated perfused mesenteries in vitro. Among these peptides SRTc demonstrated the most potent vasodilator activity, and was three times more active than SRTa in both preparations. These peptides induced endothelium-dependent vasodilatation in vitro and pretreatment with methylene blue inhibited this effect, while exposure to the antagonists of other vasodilators did not. In contrast, [nitrophenylsulfenylated Trp21]SRTc, SRTc(1-18) and reduced and S-carboxymethylated SRTc caused no vasodilatation in either animal model; the vasodilator effect of acetylated SRTc was less potent than that of SRTc. These results suggest that (i) the vasodilatations of these peptides may be exerted through the release of endothelium derived relaxing factor; (ii) the C-terminal Trp21 and disulfide bonds are essential; and (iii) the N-terminal amino group plays an important role in vasodilator activity.
在体内的自发性高血压大鼠以及体外分离灌注的大鼠肠系膜中，芋螺毒素（SRTa、SRTb和SRTc）和内皮素-1产生了强大的血管舒张作用。在这些肽中，SRTc表现出最强的血管舒张活性，在两种制剂中其活性比SRTa高两倍。这些肽在体外诱导内皮依赖性血管舒张，亚甲蓝预处理可抑制此效应，而暴露于其他血管舒张剂的拮抗剂则无此作用。相反，[硝基苯硫基化色氨酸21]SRTc、SRTc(1-18)以及还原和S-羧甲基化的SRTc在两种动物模型中均未引起血管舒张；乙酰化SRTc的血管舒张作用比SRTc弱。这些结果表明：（i）这些肽的血管舒张作用可能是通过释放内皮源性舒张因子来实现的；（ii）C末端的色氨酸21和二硫键是必不可少的；（iii）N末端氨基在血管舒张活性中起重要作用。
