{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T23:06:04Z","timestamp":1792019164533,"version":"4.4.0"},"reference-count":42,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,7,15]],"date-time":"2014-07-15T00:00:00Z","timestamp":1405382400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["STO 645\/6-1"],"award-info":[{"award-number":["STO 645\/6-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Polish Ministry of Science and Higher Education","award":["0119\/IP1\/2011\/71"],"award-info":[{"award-number":["0119\/IP1\/2011\/71"]}]},{"name":"Polish Ministry of Science and Higher Education","award":["0107\/IP1\/2013\/72"],"award-info":[{"award-number":["0107\/IP1\/2013\/72"]}]},{"name":"University of Calgary Research Grant Committee","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Diarrhea\u2010predominant irritable bowel syndrome (<jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content>\u2010D) is a functional gastrointestinal (<jats:styled-content style=\"fixed-case\">GI<\/jats:styled-content>) disorder, defined by the presence of loose stools and abdominal pain. In search for a novel anti\u2010<jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content>\u2010D therapy, here we investigated the nociceptin receptor (<jats:styled-content style=\"fixed-case\">NOP<\/jats:styled-content>)\u2010dependent effects in the <jats:styled-content style=\"fixed-case\">GI<\/jats:styled-content> tract.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A novel potent and selective <jats:styled-content style=\"fixed-case\">NOP<\/jats:styled-content> agonist <jats:styled-content style=\"fixed-case\">SCH<\/jats:styled-content> 221510 was used in the study. The effect of <jats:styled-content style=\"fixed-case\">NOP<\/jats:styled-content> activation on mouse intestinal motility was characterized <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>, in physiological conditions and in animal models of hypermotility and diarrhea. Well\u2010established mouse models of visceral pain were used to characterize the antinociceptive effect of the <jats:styled-content style=\"fixed-case\">NOP<\/jats:styled-content> activation. To provide additional evidence that the endogenous nociceptin system is a relevant target for <jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> NOP<\/jats:styled-content> expression and nociceptin levels were quantified in serum and colonic biopsies from <jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content>\u2010D patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">SCH<\/jats:styled-content> 221510 produced a potent <jats:styled-content style=\"fixed-case\">NOP<\/jats:styled-content>\u2010mediated inhibitory effect on mouse intestinal motility <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> in physiological conditions. The <jats:styled-content style=\"fixed-case\">NOP<\/jats:styled-content> agonist displayed an antidiarrheal and analgesic action after oral administration in animal models mimicking the symptoms of <jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content>\u2010D. Studies on human samples revealed a strong decrease in endogenous nociceptin system expression in <jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content>\u2010D patients compared with healthy controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>Collectively, mouse and human data suggest that the endogenous nociceptin system is involved in <jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content>\u2010D and may become a target for anti\u2010<jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content>\u2010D treatments using potent and selective synthetic <jats:styled-content style=\"fixed-case\">NOP<\/jats:styled-content> agonists.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.12390","type":"journal-article","created":{"date-parts":[[2014,7,15]],"date-time":"2014-07-15T18:24:06Z","timestamp":1405448646000},"page":"1539-1550","source":"Crossref","is-referenced-by-count":19,"title":["Activation of the endogenous nociceptin system by selective nociceptin receptor agonist <scp>SCH<\/scp> 221510 produces antitransit and antinociceptive effect: a novel strategy for treatment of diarrhea\u2010predominant <scp>IBS<\/scp>"],"prefix":"10.1111","volume":"26","author":[{"given":"J.","family":"Fichna","sequence":"first","affiliation":[{"name":"Snyder Institute for Chronic Diseases University of Calgary Calgary AB Canada"},{"name":"Division of Gastroenterology Department of Medicine University of Calgary Calgary AB Canada"},{"name":"Department of Biochemistry Medical University of Lodz Lodz Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Sobczak","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Medical University of Lodz Lodz Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Mokrowiecka","sequence":"additional","affiliation":[{"name":"Department of Digestive Tract Diseases Faculty of Medicine Medical University of Lodz Lodz Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. I.","family":"Cygankiewicz","sequence":"additional","affiliation":[{"name":"Department of Cytobiochemistry Faculty of Biology and Environmental Protection University of Lodz Lodz Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. K.","family":"Zakrzewski","sequence":"additional","affiliation":[{"name":"Department of Cytobiochemistry Faculty of Biology and Environmental Protection University of Lodz Lodz Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Cenac","sequence":"additional","affiliation":[{"name":"Inserm U1043 Toulouse France"},{"name":"CNRS U5282 Toulouse France"},{"name":"Universit\u00e9 de Toulouse, UPS Centre de Physiopathologie de Toulouse Purpan (CPTP) Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Sa\u0142aga","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Medical University of Lodz Lodz Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.\u2010P.","family":"Timmermans","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences Laboratory of Cell Biology and Histology University of Antwerp Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Vergnolle","sequence":"additional","affiliation":[{"name":"Inserm U1043 Toulouse France"},{"name":"CNRS U5282 Toulouse France"},{"name":"Universit\u00e9 de Toulouse, UPS Centre de Physiopathologie de Toulouse Purpan (CPTP) Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Ma\u0142ecka\u2010Panas","sequence":"additional","affiliation":[{"name":"Department of Digestive Tract Diseases Faculty of Medicine Medical University of Lodz Lodz Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. 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