McMahon E G, Fok K F, Moore W M, Smith C E, Siegel N R, Trapani A J
Searle Research and Development, Washington University School of Medicine, Department of Pharmacology, St. Louis, Missouri 63110.
Biochem Biophys Res Commun. 1989 Jun 15;161(2):406-13. doi: 10.1016/0006-291x(89)92613-2.
We investigated whether big endothelin (porcine 1-40) had contractile activity in isolated rat aorta or pressor activity when injected intravenously into the anesthetized rat. When isolated rat aorta was exposed to a 100 nM concentration of big endothelin, 4.8% of a maximal KCl contraction was observed, compared to 131% of KClmax when paired aortic rings were exposed to an equivalent concentration of synthetic endothelin. Likewise, big endothelin had very weak pressor activity when injected intravenously into anesthetized, ganglion-blocked rats at 10 nmol/kg. When big endothelin was incubated with chymotrypsin, native endothelin and other peptide fragments were formed. Chymotrypsin-treated big endothelin produced an endothelin-like contraction when applied to isolated rat aortic rings, and a characteristic endothelin-like effect on blood pressure in vivo. Our results indicate that the biological activity of endothelin could be effectively blocked by inhibiting the enzyme which converts big endothelin to endothelin.
我们研究了大内皮素（猪1 - 40）在离体大鼠主动脉中是否具有收缩活性，以及静脉注射到麻醉大鼠体内时是否具有升压活性。当离体大鼠主动脉暴露于100 nM浓度的大内皮素时，观察到最大氯化钾收缩的4.8%，而当配对的主动脉环暴露于同等浓度的合成内皮素时，为氯化钾最大收缩的131%。同样，当以10 nmol/kg静脉注射到麻醉的、神经节阻断的大鼠体内时，大内皮素具有非常微弱的升压活性。当大内皮素与胰凝乳蛋白酶一起孵育时，会形成天然内皮素和其他肽片段。经胰凝乳蛋白酶处理的大内皮素应用于离体大鼠主动脉环时会产生类似内皮素的收缩，并且在体内对血压产生特征性的类似内皮素的作用。我们的结果表明，通过抑制将大内皮素转化为内皮素的酶，可以有效阻断内皮素的生物活性。
