Yokokawa K, Kohno M, Yasunari K, Murakawa K, Takeda T
1st Department of Internal Medicine, Osaka City University Medical School, Japan.
Hypertension. 1991 Sep;18(3):304-15. doi: 10.1161/01.hyp.18.3.304.
Effects of endothelin-3 on the secretion of endothelin-1 and other endothelium-derived substances were investigated in cultured human umbilical vein endothelial cells. The present binding study showed two distinct subpopulations of binding sites for endothelin-3 with higher and lower affinities in cultured human endothelial cells. Endothelin-3 caused an increase in intracellular Ca2+ and inositol 1,4,5-trisphosphate levels and activated protein kinase C in a dose-dependent manner. Endothelin-3 also caused an increase in [3H]thymidine incorporation into cellular DNA and stimulated the production of cyclic guanosine 3',5'-monophosphate, 6-ketoprostaglandin F1 alpha, and immunoreactive endothelin-1 in cultured human endothelial cells. NG-Monomethyl L-arginine (3 x 10(-4) mol/l) and indomethacin (10(-5) mol/l) enhanced endothelin-3-induced endothelin-1 production. These results suggest that endothelin-3 bound to its specific receptors and then caused phosphoinositide breakdown, subsequently mobilizing intracellular Ca2+ and leading to protein kinase C activation and the initiation of DNA synthesis, resulting in the stimulation of endothelin-1 production by human endothelial cells. Furthermore, this endothelin-1 production may be suppressed by endothelium-derived relaxing factor and prostacyclin produced in response to endothelin-3 in cultured human endothelial cells.
在内皮细胞中研究了内皮素-3对内皮素-1及其他内皮源性物质分泌的影响。目前的结合研究表明，在培养的人内皮细胞中，内皮素-3有两个不同的结合位点亚群，亲和力有高有低。内皮素-3以剂量依赖的方式导致细胞内钙离子和肌醇1,4,5-三磷酸水平升高，并激活蛋白激酶C。内皮素-3还使培养的人内皮细胞中[3H]胸腺嘧啶核苷掺入细胞DNA增加，并刺激环磷酸鸟苷、6-酮前列腺素F1α和免疫反应性内皮素-1的产生。NG-单甲基-L-精氨酸（3×10(-4)mol/L）和吲哚美辛（10(-5)mol/L）增强了内皮素-3诱导的内皮素-1产生。这些结果表明，内皮素-3与其特异性受体结合，然后导致磷酸肌醇分解，随后动员细胞内钙离子并导致蛋白激酶C激活以及DNA合成启动，从而刺激人内皮细胞产生内皮素-1。此外，在培养的人内皮细胞中，这种内皮素-1的产生可能会被内皮源性舒张因子和前列环素抑制，它们是对内皮素-3产生的反应。
