Yamada K, Goto A, Sugimoto T
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
J Cardiovasc Pharmacol. 1991;17 Suppl 7:S163-4. doi: 10.1097/00005344-199100177-00045.
We have recently isolated two endogenous digitalis-like factors (EDLFs) from human urine. The polar EDLF (ouabain-displacing compound 1; ODC-1) fulfills the criteria for the putative natriuretic and vasoactive digitalis-like factor. In this study, we examined the effects of ODC-1 and ouabain on endothelin-1 (ET-1) secretion from cultured endothelial cells. ODC-1 was partially purified from human urine with use of reverse-phase HPLC based on the inhibitory effects on [3H]ouabain binding to intact human erythrocytes. A serial dilution curve of the extract of the serum-free culture medium from CPAE (bovine pulmonary artery endothelium) cells was parallel to that of standard ET-1. Immunoreactive (ir-) ET-1 was secreted in a linear fashion over 5 h from CPAE cells. ODC-1 stimulated ET-1 secretion in a dose-dependent manner. In contrast, ouabain did not affect ET-1 secretion at the concentration of 10(-9)-10(-5) M. These results indicate that human urine-derived ODC-1 is distinct from plant-derived ouabain and acts as a stimulator of ET-1 secretion, and also suggest that ODC-1 may play an important role as a direct and indirect modulator of vascular tone.
我们最近从人尿中分离出了两种内源性洋地黄样因子（EDLFs）。极性EDLF（哇巴因置换化合物1；ODC-1）符合假定的利钠和血管活性洋地黄样因子的标准。在本研究中，我们检测了ODC-1和哇巴因对培养的内皮细胞分泌内皮素-1（ET-1）的影响。基于对[3H]哇巴因与完整人红细胞结合的抑制作用，利用反相高效液相色谱法从人尿中部分纯化了ODC-1。CPAE（牛肺动脉内皮）细胞无血清培养基提取物的系列稀释曲线与标准ET-1的曲线平行。免疫反应性（ir-）ET-1在5小时内以线性方式从CPAE细胞中分泌出来。ODC-1以剂量依赖性方式刺激ET-1分泌。相比之下，在10^(-9)-10^(-5) M的浓度下，哇巴因不影响ET-1分泌。这些结果表明，源自人尿的ODC-1与源自植物的哇巴因不同，可作为ET-1分泌的刺激物，也提示ODC-1可能作为血管张力的直接和间接调节剂发挥重要作用。
