Effect of endogenous digitalis-like factor on endothelin secretion from bovine endothelial cells.
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.
Yamada
K
K
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Goto
A
A
Sugimoto
T
T
D000818:Animals; D002298:Cardenolides; D002417:Cattle; D002478:Cells, Cultured; D004077:Digoxin; D016232:Endothelins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D010042:Ouabain / Q000097:blood / Q000494:pharmacology; D011863:Radioimmunoassay; D012503:Saponins; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000494:pharmacology
D002298:Cardenolides; D016232:Endothelins; D012503:Saponins; C034504:digoxin-like factors; D010042:Ouabain; D004077:Digoxin; D000254:Sodium-Potassium-Exchanging ATPase