{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T11:03:57Z","timestamp":1785927837576,"version":"3.56.0"},"reference-count":58,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2009,1,30]],"date-time":"2009-01-30T00:00:00Z","timestamp":1233273600000},"content-version":"vor","delay-in-days":1796,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2004,3]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Gastro\u2010oesophageal acid reflux may cause airway responses such as cough, bronchoconstriction and inflammation in asthmatic patients. Our previous results suggest that microvascular leakage induced, in the guinea\u2010pig airways, by intra\u2010oesophageal hydrochloric acid (HCl) infusion was mainly dependent on the release of tachykinins. Nociceptin, an endogenous ligand of the opioid receptor NOP, has been shown to inhibit bronchoconstriction and cough in guinea\u2010pig or cat by inhibiting tachykinin release.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The purpose of this study was to investigate the effects of nociceptin on the intra\u2010oesophageal HCl\u2010induced airway microvascular leakage evaluated by Evans blue dye extravasation measurement in anaesthetised guinea\u2010pigs pretreated with propranolol, atropine and phosphoramidon.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Infusion of intra\u2010oesophageal HCl led to a significant increase in plasma extravasation in the main bronchi and trachea. This increase was abolished when animals underwent a bilateral vagotomy.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Airway microvascular leakage was inhibited by nociceptin (3\u201330 <jats:italic>\u03bc<\/jats:italic>g kg<jats:sup>\u22121<\/jats:sup> i.v.) in a dose\u2010dependent manner (maximal inhibition at the dose of 30 <jats:italic>\u03bc<\/jats:italic>g kg<jats:sup>\u22121<\/jats:sup>: 19.76\u00b11.13 vs 90.92\u00b114.00 ng mg<jats:sup>\u22121<\/jats:sup> tissue for nociceptin and HCl infusion, respectively, in the main bronchi, <jats:italic>P<\/jats:italic>&lt;0.01). The NOP receptor agonist [Arg<jats:sup>14<\/jats:sup>,Lys<jats:sup>15<\/jats:sup>]N\/OFQ mimicked the inhibitory effect of nociceptin, but at a 10\u2010fold lower dose (3 <jats:italic>\u03bc<\/jats:italic>g kg<jats:sup>\u22121<\/jats:sup> i.v). The NOP receptor antagonist J\u2010113397 had no effect on plasma protein extravasation by itself, but was able to block the inhibitory effect of nociceptin.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Morphine (1 mg kg<jats:sup>\u22121<\/jats:sup>) had a similar inhibitory effect as that of nociceptin. Naloxone pretreatment abolished the effect of morphine, but was enable to block the inhibitory effect of nociceptin.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Under similar conditions, nociceptin, in the previous range of concentration, was unable to counteract the airway microvascular leakage induced by substance P (SP).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results suggest that airway plasma extravasation induced by intra\u2010oesophageal HCl instillation might be inhibited by specific stimulation of the NOP receptor with nociceptin. Nociceptin is likely to act at a pre\u2010junctional level, by inhibiting tachykinin release, since it was unable to prevent SP\u2010induced airway plasma extravasation.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2004) <jats:bold>141<\/jats:bold>, 1077\u20131083. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0705704\">10.1038\/sj.bjp.0705704<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0705704","type":"journal-article","created":{"date-parts":[[2004,3,17]],"date-time":"2004-03-17T17:13:07Z","timestamp":1079543587000},"page":"1077-1083","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Nociceptin inhibits airway microvascular leakage induced by HCl intra\u2010oesophageal instillation"],"prefix":"10.1111","volume":"141","author":[{"given":"C\u00e9line","family":"Rouget","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong Yao","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"D'Agostino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Faisy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Naline","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Bardou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Advenier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,30]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"51","volume-title":"Experimental and Clinical Pharmacology of Gastroesophageal Reflux\u2010induced Asthma","author":"ADVENIER C.","year":"2002"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19960429)368:2<229::AID-CNE5>3.0.CO;2-5"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1542\/peds.68.1.29","article-title":"Gastroesophageal reflux\u2010associated recurrent pneumonia and chronic asthma in children","volume":"68","author":"BERQUIST W.E.","year":"1981","journal-title":"Pediatrics"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002100000220"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(01)01244-4"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(94)00561-3"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703219"},{"key":"e_1_2_7_9_1","first-page":"370","article-title":"Pharmacological analysis of the tachykinin receptors that mediate activation of nonadrenergic, noncholinergic relaxant nerves that innervate guinea pig trachealis","volume":"284","author":"CANNING B.J.","year":"1998","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2001.91.6.2642"},{"key":"e_1_2_7_11_1","first-page":"L698","article-title":"Effects of organotypic culture on parasympathetic innervation of guinea pig trachealis","volume":"271","author":"CANNING B.J.","year":"1996","journal-title":"Am. J. Physiol."},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0163-7258(89)90021-1"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.31.4.370"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(00)00505-7"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.02.00250902"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(01)00460-2"},{"key":"e_1_2_7_17_1","first-page":"A148","article-title":"Nociceptin inhibits the in vitro fenoterol\u2010induced neurosensitization of human bronchi","volume":"167","author":"FAISY C.","year":"2003","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"e_1_2_7_18_1","first-page":"902","article-title":"Nociceptin\u2010induced inhibition of tachykinergic neurotransmission in guinea pig bronchus","volume":"285","author":"FISCHER A.","year":"1998","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119039"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(02)02372-X"},{"key":"e_1_2_7_21_1","first-page":"306","article-title":"Assessment of a technique for scintigraphic monitoring of pulmonary aspiration of gastric contents in asthmatics with gastroesophageal reflux","volume":"42","author":"GHAED N.","year":"1979","journal-title":"Ann. Allergy"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1997.82.3.738"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9270(00)01075-3"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1164\/arrd.1986.134.5.986"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.46.7.479"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/140.5.1294"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1999.86.4.1226"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704515"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(00)00357-2"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm990517p"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1475-097X.1981.tb00897.x"},{"key":"e_1_2_7_32_1","first-page":"431","article-title":"The role of the vague nerve in airway narrowing caused by intraesophageal hydrochloric acid provocation and esophageal distention","volume":"47","author":"MANSFIELD L.E.","year":"1981","journal-title":"Ann. Allergy"},{"key":"e_1_2_7_33_1","first-page":"224","article-title":"Gastroesophageal reflux and asthma: a possible reflex mechanism","volume":"41","author":"MANSFIELD L.E.","year":"1978","journal-title":"Ann. Allergy"},{"key":"e_1_2_7_34_1","first-page":"255","article-title":"Microinjection of nociceptin (Orphanin FQ) into nucleus tractus solitarii elevates blood pressure and heart rate in both anesthetized and conscious rats","volume":"294","author":"MAO L.","year":"2000","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(00)00370-5"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1995.sp020747"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00007.2002"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702522"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1681.2000.03365.x"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703954"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(97)01411-8"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/377532a0"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-0115(01)00309-3"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(94)80235-1"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2000.279.4.R1215"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-1838(96)00081-1"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1993.sp019881"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(98)00216-7"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1139\/cjpp-76-3-304"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-9781(00)00240-0"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(00)00520-3"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701013"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5237.792"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(01)00816-6"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.300.1.57"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1988.tb11745.x"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-6749(82)90176-2"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1080\/00365520310002490"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(84)90082-9"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0705704","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0705704","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/sj.bjp.0705704","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T16:22:08Z","timestamp":1697214128000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1038\/sj.bjp.0705704"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,3]]},"references-count":58,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2004,3]]}},"alternative-id":["10.1038\/sj.bjp.0705704"],"URL":"https:\/\/doi.org\/10.1038\/sj.bjp.0705704","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,3]]},"assertion":[{"value":"2009-01-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}