{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:20:54Z","timestamp":1791220854469,"version":"4.1.0"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[1991,9]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1161\/01.hyp.18.3.304","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:24:03Z","timestamp":1339460643000},"page":"304-315","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":58,"title":["Endothelin-3 regulates endothelin-1 production in cultured human endothelial cells."],"prefix":"10.1161","volume":"18","author":[{"given":"K","family":"Yokokawa","sequence":"first","affiliation":[{"name":"1st Department of Internal Medicine, Osaka City University Medical School, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Kohno","sequence":"additional","affiliation":[{"name":"1st Department of Internal Medicine, Osaka City University Medical School, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Yasunari","sequence":"additional","affiliation":[{"name":"1st Department of Internal Medicine, Osaka City University Medical School, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Murakawa","sequence":"additional","affiliation":[{"name":"1st Department of Internal Medicine, Osaka City University Medical School, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Takeda","sequence":"additional","affiliation":[{"name":"1st Department of Internal Medicine, Osaka City University Medical School, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","container-title":["Hypertension"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/pdf\/10.1161\/01.HYP.18.3.304","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T17:16:26Z","timestamp":1715534186000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.HYP.18.3.304"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1991,9]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1991,9]]}},"alternative-id":["10.1161\/01.HYP.18.3.304"],"URL":"https:\/\/doi.org\/10.1161\/01.hyp.18.3.304","relation":{},"ISSN":["0194-911X","1524-4563"],"issn-type":[{"value":"0194-911X","type":"print"},{"value":"1524-4563","type":"electronic"}],"subject":[],"published":{"date-parts":[[1991,9]]},"assertion":[{"value":"1991-09-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}