{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:40:41Z","timestamp":1790815241558,"version":"4.1.0"},"reference-count":40,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2011,7]]},"abstract":"<jats:p> Neutral sphingomyelinase (nSMase)-derived ceramide has been proposed as a mediator of hypoxic pulmonary vasoconstriction (HPV), a specific response of the pulmonary circulation. Voltage-gated K<jats:sup>+<\/jats:sup> (K<jats:sub>v<\/jats:sub>) channels are modulated by numerous vasoactive factors, including hypoxia, and their inhibition has been involved in HPV. Herein, we have analyzed the effects of ceramide on K<jats:sub>v<\/jats:sub> currents and contractility in rat pulmonary arteries (PA) and in mesenteric arteries (MA). The ceramide analog C6-ceramide inhibited K<jats:sub>v<\/jats:sub> currents in PA smooth muscle cells (PASMC). Similar effects were obtained after the addition of bacterial sphingomyelinase (SMase), indicating a role for endogenous ceramide in K<jats:sub>v<\/jats:sub> channel regulation. K<jats:sub>v<\/jats:sub> current was reduced by stromatoxin and diphenylphosphine oxide-1 (DPO-1), selective inhibitors of K<jats:sub>v<\/jats:sub>2.1 and K<jats:sub>v<\/jats:sub>1.5 channels, respectively. The inhibitory effect of ceramide was still present in the presence of stromatoxin or DPO-1, suggesting that this sphingolipid inhibited both components of the native K<jats:sub>v<\/jats:sub> current. Accordingly, ceramide inhibited K<jats:sub>v<\/jats:sub>1.5 and K<jats:sub>v<\/jats:sub>2.1 channels expressed in Ltk<jats:sup>\u2212<\/jats:sup> cells. Ceramide-induced effects were reduced in human embryonic kidney 293 cells expressing K<jats:sub>v<\/jats:sub>1.5 channels but not the regulatory subunit K<jats:sub>v<\/jats:sub>\u03b22.1. The nSMase inhibitor GW4869 reduced the thromboxane-endoperoxide receptor agonist U46619-induced, but not endothelin-1-induced pulmonary vasoconstriction that was partly restored after addition of exogenous ceramide. The PKC-\u03b6 pseudosubstrate inhibitor (PKC\u03b6-PI) inhibited the K<jats:sub>v<\/jats:sub> inhibitory and contractile effects of ceramide. In MA ceramide had no effect on K<jats:sub>v<\/jats:sub> currents and GW4869 did not affect U46619-induced contraction. The effects of SMase were also observed in human PA. These results suggest that ceramide represents a crucial signaling mediator in the pulmonary vasculature. <\/jats:p>","DOI":"10.1152\/ajpcell.00243.2010","type":"journal-article","created":{"date-parts":[[2011,4,14]],"date-time":"2011-04-14T02:07:39Z","timestamp":1302746859000},"page":"C186-C194","source":"Crossref","is-referenced-by-count":29,"title":["Ceramide inhibits K<sub>v<\/sub> currents and contributes to TP-receptor-induced vasoconstriction in rat and human pulmonary arteries"],"prefix":"10.1152","volume":"301","author":[{"given":"Javier","family":"Moral-Sanz","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Universidad Complutense Madrid;"},{"name":"Centro de Investigaciones Biomedicas en Red de Enfermedades Respiratorias (CIBERES);"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas \u201cAlberto Sols\u201d Consejo Superior de Investigaciones Cient\u00edficas-Universidad Aut\u00f3noma de Madrid, Madrid; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Menendez","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Universidad Complutense Madrid;"},{"name":"Centro de Investigaciones Biomedicas en Red de Enfermedades Respiratorias (CIBERES);"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miren","family":"David","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas \u201cAlberto Sols\u201d Consejo Superior de Investigaciones Cient\u00edficas-Universidad Aut\u00f3noma de Madrid, Madrid; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Moreno","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Universidad Complutense Madrid;"},{"name":"Centro de Investigaciones Biomedicas en Red de Enfermedades Respiratorias (CIBERES);"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvaro","family":"Macias","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas \u201cAlberto Sols\u201d Consejo Superior de Investigaciones Cient\u00edficas-Universidad Aut\u00f3noma de Madrid, Madrid; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Cortijo","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biomedicas en Red de Enfermedades Respiratorias (CIBERES);"},{"name":"Department of Pharmacology, Faculty of Medicine, University of Valencia. Fundaci\u00f3n Investigaci\u00f3n, Hospital General Universitario de Valencia,Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Valenzuela","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas \u201cAlberto Sols\u201d Consejo Superior de Investigaciones Cient\u00edficas-Universidad Aut\u00f3noma de Madrid, Madrid; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Perez-Vizcaino","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Universidad Complutense Madrid;"},{"name":"Centro de Investigaciones Biomedicas en Red de Enfermedades Respiratorias (CIBERES);"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel","family":"Cogolludo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Universidad Complutense Madrid;"},{"name":"Centro de Investigaciones Biomedicas en Red de Enfermedades Respiratorias (CIBERES);"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.00-0649fje"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI333"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000137173.42723.fb"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M007346200"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000095245.97945.FE"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvn349"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000216858.04599.e1"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2004.12.019"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1159\/000097754"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00462.2009"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5433.1565"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1124\/mol.62.6.1456"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00416.2005"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.14.7661"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(02)00411-X"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2003.08.004"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0216127"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.101162"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1161\/hh2301.100350"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.33.6.1441"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M206747200"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/S1050-1738(00)00037-2"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1042\/bj3350465"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000145360.16770.9f"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1124\/mol.107.037002"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1995.tb07188.x"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000154070.06421.25"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00028.2005"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000062688.76508.B3"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvp143"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2004.05.007"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1021\/tx0341097"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.2001.281.5.L1115"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.5.2406"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.94.3.562"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199703000-00025"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2006.04.014"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.77.2.370"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1993.264.2.L116"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.278.5.H1421"}],"container-title":["American Journal of Physiology-Cell Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpcell.00243.2010","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T16:59:02Z","timestamp":1718643542000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpcell.00243.2010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,7]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2011,7]]}},"alternative-id":["10.1152\/ajpcell.00243.2010"],"URL":"https:\/\/doi.org\/10.1152\/ajpcell.00243.2010","relation":{},"ISSN":["0363-6143","1522-1563"],"issn-type":[{"value":"0363-6143","type":"print"},{"value":"1522-1563","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,7]]}}}