人组织蛋白酶产生的一种新型血管收缩产物——31个氨基酸长度的内皮素-1可促使内皮细胞生成一氧化氮。

Production of nitric oxide from endothelial cells by 31-amino-acid-length endothelin-1, a novel vasoconstrictive product by human chymase.

作者信息

Niwa Y, Nagata N, Oka M, Toyoshima T, Akiyoshi H, Wada T, Nakaya Y

机构信息

Department of Nutrition, The University of Tokushima, School of Medicine, Japan.

出版信息

Life Sci. 2000;67(9):1103-9. doi: 10.1016/s0024-3205(00)00700-1.

DOI:10.1016/s0024-3205(00)00700-1

PMID:10954044

Abstract

Human chymase selectively converts big endothelin (ET)-1 to 31-amino-acid-length ET-1 [ET-1(1-31)]. In this study we examined effect of ET-1(1-31) on endothelial function. ET-1(1-31) evoked contraction in a concentration-dependent manner at > 10(-8) M, which was about 10 times weaker than that of conventional ET-1 [ET-1(1-21)]. BQ485, an ETA receptor antagonist, completely abolished ET-1(1-31)-induced contraction, but BQ788, an ETB receptor antagonist, slightly enhanced it, suggesting that ET-1(1-31) relaxes artery via endothelium. On endothelial cells, ET-1(1-21) and ET-1(1-31) increased [Ca2+]i and produced NO, both of which were significantly inhibited by BQ788 and not by BQ485. These results indicate that ET-1(1-31) increased [Ca2+]i and produced NO in endothelial cells through ETB receptor similarly with ET-1(1-21), although slight difference in effect on smooth muscle cells.

摘要

人糜蛋白酶可将大内皮素（ET）-1选择性转化为31个氨基酸长度的ET-1 [ET-1(1-31)]。在本研究中，我们检测了ET-1(1-31)对内皮功能的影响。ET-1(1-31)在浓度大于10(-8) M时以浓度依赖性方式引起收缩，其收缩作用比传统的ET-1 [ET-1(1-21)]弱约10倍。ETA受体拮抗剂BQ485完全消除了ET-1(1-31)诱导的收缩，但ETB受体拮抗剂BQ788却使其略有增强，这表明ET-1(1-31)通过内皮使动脉舒张。在内皮细胞上，ET-1(1-21)和ET-1(1-31)均可增加细胞内钙离子浓度（[Ca2+]i）并产生一氧化氮（NO），两者均被BQ788显著抑制，而不被BQ485抑制。这些结果表明，ET-1(1-31)与ET-1(1-21)类似，通过ETB受体在内皮细胞中增加[Ca2+]i并产生NO，尽管其对平滑肌细胞的作用存在细微差异。