{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:36:24Z","timestamp":1790516184000,"version":"4.1.0"},"reference-count":62,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,10,31]],"date-time":"2019-10-31T00:00:00Z","timestamp":1572480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007150","name":"United Therapeutics Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007150","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>In patients with pulmonary hypertension (PH) associated with lung disease and\/or hypoxia (Group III), decreased pulmonary vascular tone and tissue hypoxia is therapeutically beneficial. PGE<jats:sub>2<\/jats:sub> and PGI<jats:sub>2<\/jats:sub> induce potent relaxation of human bronchi from non\u2010PH (control) patients via EP<jats:sub>4<\/jats:sub> and IP receptors, respectively. However, the effects of PGE<jats:sub>2<\/jats:sub>\/PGI<jats:sub>2<\/jats:sub> and their mimetics on human bronchi from PH patients are unknown. Here, we have compared relaxant effects of several PGI<jats:sub>2<\/jats:sub>\u2013mimetics approved for treating PH Group I with several PGE<jats:sub>2<\/jats:sub>\u2013mimetics, in bronchial preparations derived from PH Group III and control patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Relaxation of bronchial muscle was assessed in samples isolated from control and PH Group III patients. Expression of prostanoid receptors was analysed by western blot and real\u2010time PCR, and endogenous PGE<jats:sub>2<\/jats:sub>, PGI<jats:sub>2<\/jats:sub>, and cAMP levels were determined by ELISA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Maximal relaxations induced by different EP<jats:sub>4<\/jats:sub> receptor agonists (PGE<jats:sub>2<\/jats:sub>, L\u2010902688, and ONO\u2010AE1\u2010329) were decreased in human bronchi from PH patients, compared with controls. However, maximal relaxations produced by PGI<jats:sub>2<\/jats:sub>\u2013mimetics (iloprost, treprostinil, and beraprost) were similar for both groups of patients. Both EP<jats:sub>4<\/jats:sub> and IP receptor protein and mRNA expressions were significantly lower in human bronchi from PH patients. cAMP levels significantly correlated with PGI<jats:sub>2<\/jats:sub> but not with PGE<jats:sub>2<\/jats:sub> levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>The PGI<jats:sub>2<\/jats:sub>\u2013mimetics retained maximal bronchodilation in PH Group III patients, whereas bronchodilation induced by EP<jats:sub>4<\/jats:sub> receptor agonists was decreased. Restoration of EP<jats:sub>4<\/jats:sub> receptor expression in airways of PH Group III patients with respiratory diseases could bring additional therapeutic benefit.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14854","type":"journal-article","created":{"date-parts":[[2019,9,2]],"date-time":"2019-09-02T13:53:52Z","timestamp":1567432432000},"page":"161-174","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Bronchodilation induced by PGE<sub>2<\/sub> is impaired in Group III pulmonary hypertension"],"prefix":"10.1111","volume":"177","author":[{"given":"Gulsev","family":"Ozen","sequence":"first","affiliation":[{"name":"INSERM U1148 H\u00f4pital Bichat  Paris France"},{"name":"Faculty of Pharmacy, Department of Pharmacology Istanbul University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chabha","family":"Benyahia","sequence":"additional","affiliation":[{"name":"INSERM U1148 H\u00f4pital Bichat  Paris France"},{"name":"Paris 13 University (USPC)  Villetaneuse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salma","family":"Mani","sequence":"additional","affiliation":[{"name":"INSERM U1148 H\u00f4pital Bichat  Paris France"},{"name":"Paris 13 University (USPC)  Villetaneuse France"},{"name":"Institut Sup\u00e9rieur de Biotechnologie de Monastir (ISBM) Universit\u00e9 de Monastir  Monastir Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamel","family":"Boukais","sequence":"additional","affiliation":[{"name":"INSERM U1148 H\u00f4pital Bichat  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam M.","family":"Silverstein","sequence":"additional","affiliation":[{"name":"United Therapeutics  Research Triangle Park NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Bayles","sequence":"additional","affiliation":[{"name":"INSERM U1148 H\u00f4pital Bichat  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew C.","family":"Nelsen","sequence":"additional","affiliation":[{"name":"United Therapeutics  Research Triangle Park NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Castier","sequence":"additional","affiliation":[{"name":"H\u00f4pital Bichat\u2010Claude Bernard, AP\u2010HP, Paris Diderot University Universit\u00e9 de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Danel","sequence":"additional","affiliation":[{"name":"H\u00f4pital Bichat\u2010Claude Bernard, AP\u2010HP, Paris Diderot University Universit\u00e9 de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herv\u00e9","family":"Mal","sequence":"additional","affiliation":[{"name":"H\u00f4pital Bichat\u2010Claude Bernard, AP\u2010HP, Paris Diderot University Universit\u00e9 de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie H.","family":"Clapp","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Science University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Longrois","sequence":"additional","affiliation":[{"name":"INSERM U1148 H\u00f4pital Bichat  Paris France"},{"name":"Paris 13 University (USPC)  Villetaneuse France"},{"name":"H\u00f4pital Bichat\u2010Claude Bernard, AP\u2010HP, Paris Diderot University Universit\u00e9 de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0734-3359","authenticated-orcid":false,"given":"Xavier","family":"Norel","sequence":"additional","affiliation":[{"name":"INSERM U1148 H\u00f4pital Bichat  Paris France"},{"name":"Paris 13 University (USPC)  Villetaneuse France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,10,31]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1388-1981(99)00164-X"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13878"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2005-0289OC"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2012-0158OC"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1086\/689291"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2009-0017"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prostaglandins.2013.07.001"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2011.12.012"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2011.08.019"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2014-206592"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/1755-5922.12008"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510562103"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2010.158568"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prostaglandins.2015.04.007"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M502242200"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14153"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1159\/000242498"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201001-0011OC"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.90391.2008"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm5090075"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.83.5.732"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv317"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2017.06.008"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1121"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0090-6980(87)90113-4"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.08-1515"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201501-020AS"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2009.09.005"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00130408"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(15)00542-1"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24084"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00562439"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-09-0511"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-016-0409-0"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200710-1519OC"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11096-013-9762-3"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.109.156398"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.01.027"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.149.5.8173753"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1136\/thorax.57.6.473"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2011.03.001"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702392"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.160.2.9810008"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2004.01.003"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19082372"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/148.1.87"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2017.03.003"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00238.2014"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2003.09.031"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2006.05.019"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1086\/679722"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.04.002"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2013-204150"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.152.4.7551393"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1981.tb01297.x"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.50.5995"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01913-2018"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702383"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2006.06.062"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.37.6.430"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2012.03.012"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.14854","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bph.14854","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.14854","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,3]],"date-time":"2023-09-03T11:55:57Z","timestamp":1693742157000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.14854"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,31]]},"references-count":62,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,1]]}},"alternative-id":["10.1111\/bph.14854"],"URL":"https:\/\/doi.org\/10.1111\/bph.14854","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,31]]},"assertion":[{"value":"2019-05-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}