{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:18:14Z","timestamp":1791310694278,"version":"4.3.1"},"reference-count":39,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2009,1]]},"abstract":"<jats:p>\n                    Human cytochrome P-450 epoxygenase enzymes metabolize eicosapentaenoic acid (EPA), an \u03c9-3-polyunsaturated fatty acid (PUFA), and leads to the production of 17(18)-epoxyeicosatetraenoic acid, or 17(18)-EpETE. The aim of the present study was to delineate the mode of action of 17(18)-EpETE on human pulmonary artery (HPA) and distal bronchi. Isometric tension measurements demonstrated that 17(18)-EpETE induced concentration-dependent relaxing effects in pulmonary artery and airway smooth muscles. Iberiotoxin (IbTx) and glyburide (Glyb), known BK\n                    <jats:sub>Ca<\/jats:sub>\n                    and K\n                    <jats:sub>ATP<\/jats:sub>\n                    channel inhibitors, respectively, reversed the relaxation induced by 17(18)-EpETE on both tissues types. Microelectrode measurements showed that exogenous addition of 17(18)-EpETE hyperpolarized the membrane potential of HPA and bronchial smooth muscle cells. These induced electrophysiological effects were reversed by the addition of 10 nM IbTx and 10 \u03bcM Glyb. Complementary experiments performed on human bronchi, using the planar lipid bilayer reconstitution technique, demonstrated that 17(18)-EpETE activated reconstituted BK\n                    <jats:sub>Ca<\/jats:sub>\n                    channels at low free Ca\n                    <jats:sup>2+<\/jats:sup>\n                    concentration. Moreover, in bronchi, the relaxing responses induced by 17(18)-EpETE were also related to reduced Ca\n                    <jats:sup>2+<\/jats:sup>\n                    sensitivity of the myofilaments, since free Ca\n                    <jats:sup>2+<\/jats:sup>\n                    concentration-response curves, performed on \u03b2-escin-permeabilized cultured explants, were shifted toward higher Ca\n                    <jats:sup>2+<\/jats:sup>\n                    . Together, these results provide new insight into the mode of action of 17(18)-EpETE in lung tissues and highlight this eicosanoid as a potent modulator of tone on both HPA and distal bronchi in vitro, which may be of clinical relevance in the pathophysiology of pulmonary hypertension and airway diseases.\n                  <\/jats:p>","DOI":"10.1152\/ajplung.90436.2008","type":"journal-article","created":{"date-parts":[[2008,10,31]],"date-time":"2008-10-31T20:55:04Z","timestamp":1225486504000},"page":"L130-L139","source":"Crossref","is-referenced-by-count":77,"title":["Relaxing effects of 17(18)-EpETE on arterial and airway smooth muscles in human lung"],"prefix":"10.1152","volume":"296","author":[{"given":"Caroline","family":"Morin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Sirois","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Echave","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edmond","family":"Rizcallah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Rousseau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(01)00406-0"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.2500\/108854194778702874"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.2001.280.5.L965"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2007.10.028"},{"key":"R5","doi-asserted-by":"crossref","unstructured":"Capdevila JH\n                      , Falck JR, Harris RC.\n                      Cytochrome P450 and arachidonic acid bioactivation. Molecular and functional properties of the arachidonate monooxygenase.\n                      J Lipid Res\n                      41\n                      : 163\u2013181, 2000.","DOI":"10.1016\/S0022-2275(20)32049-6"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/71.1.171S"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198902023200501"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1038\/46816"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1126\/science.294.5548.1871"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2005.10.007"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2007.038166"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.92.308"},{"key":"R13","doi-asserted-by":"crossref","unstructured":"Jacobs ER\n                      , Zeldin DC.\n                      The lung HETEs (and EETs) up.\n                      Am J Physiol Heart Circ Physiol\n                      280\n                      : H1\u2013H10, 2001.","DOI":"10.1152\/ajpheart.2001.280.1.H1"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000038493.65177.94"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00927.2005"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1161\/hy0202.103293"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.2500\/108854191778879070"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(97)00838-2"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2007-0232OC"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2006-0281OC"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00125.2007"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1999.276.6.R1691"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5431.1276"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjhyper.2004.08.030"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00021.2001"},{"key":"R26","doi-asserted-by":"crossref","unstructured":"Sakai H\n                      , Chiba Y, Hirano T, Misawa M.\n                      Possible involvement of CPI-17 in augmented bronchial smooth muscle contraction in antigen-induced airway hyper-responsive rats.\n                      Mol Pharmacol\n                      68\n                      : 145\u2013151, 2005.","DOI":"10.1124\/mol.104.004325"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2003.12.023"},{"key":"R28","unstructured":"Simopoulos AP\n                      .\n                      Essential fatty acids in health and chronic diseases.\n                      Forum Nutr\n                      56\n                      : 67\u201370, 2003."},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1080\/07315724.2002.10719248"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00023.2003"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00402.2006"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1038\/40187"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4165(88)90137-7"},{"key":"R34","unstructured":"Wang MH\n                      , Brand-Schieber E, Zand BA, Nguyen X, Falck JR, Balu N, Schwartzman ML.\n                      Cytochrome P450-derived arachidonic acid metabolism in the rat kidney: characterization of selective inhibitors.\n                      J Pharmacol Exp Ther\n                      284\n                      : 966\u2013973, 1998."},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1007\/s00359-002-0281-2"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.303.2.768"},{"key":"R37","unstructured":"Zeldin DC\n                      , Foley J, Ma J, Boyle JE, Pascual JM, Moomaw CR, Tomer KB, Steenbergen C, Wu S.\n                      CYP2J subfamily P450s in the lung: expression, localization, and potential functional significance.\n                      Mol Pharmacol\n                      50\n                      : 1111\u20131117, 1996."},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2001.280.6.H2430"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2006.04.002"}],"container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajplung.90436.2008","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,19]],"date-time":"2021-09-19T17:02:37Z","timestamp":1632070957000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajplung.90436.2008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,1]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2009,1]]}},"alternative-id":["10.1152\/ajplung.90436.2008"],"URL":"https:\/\/doi.org\/10.1152\/ajplung.90436.2008","relation":{},"ISSN":["1040-0605","1522-1504"],"issn-type":[{"value":"1040-0605","type":"print"},{"value":"1522-1504","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,1]]}}}