{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:35:57Z","timestamp":1790516157499,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"S4","license":[{"start":{"date-parts":[[2014,12,18]],"date-time":"2014-12-18T00:00:00Z","timestamp":1418860800000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aim<\/jats:title><jats:p>We investigated the roles of cyclooxygenase (<jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>) isozymes and prostaglandins (<jats:styled-content style=\"fixed-case\">PGs<\/jats:styled-content>) and their receptors in mucosal defense against cold\u2010restraint stress (<jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>)\u2010induced gastric lesions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6 wild\u2010type (<jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>) mice and those lacking<jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>\u20101 or<jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>\u20102 as well as those lacking<jats:styled-content style=\"fixed-case\">EP<\/jats:styled-content>1,<jats:styled-content style=\"fixed-case\">EP<\/jats:styled-content>3, or<jats:styled-content style=\"fixed-case\">IP<\/jats:styled-content>receptors were used after 18\u2009h fasting. Animals were restrained in Bollman cages and kept in a cold room at 10\u00b0C for 90\u2009min.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>induced multiple hemorrhagic lesions in<jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>mouse stomachs. The severity of these lesions was significantly worsened by pretreatment with the nonselective<jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>inhibitors (indomethacin, loxoprofen) or selective<jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>\u20101 inhibitor (<jats:styled-content style=\"fixed-case\">SC<\/jats:styled-content>\u2010560), while neither of the selective<jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>\u20102 inhibitors (rofecoxib and celecoxib) had any effect. These lesions were also aggravated in animals lacking<jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>\u20101, but not<jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>\u20102. The expression of<jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>\u20102\u2009m<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>was not detected in the stomach after<jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>, while<jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>\u20101 expression was observed under normal and stressed conditions. The gastric ulcerogenic response to<jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>was similar between<jats:styled-content style=\"fixed-case\">EP<\/jats:styled-content>1 or<jats:styled-content style=\"fixed-case\">EP<\/jats:styled-content>3 knockout mice and<jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>mice, but was markedly worsened in animals lacking<jats:styled-content style=\"fixed-case\">IP<\/jats:styled-content>receptors. Pretreating<jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>mice with iloprost (the<jats:styled-content style=\"fixed-case\">PGI<\/jats:styled-content><jats:sub>2<\/jats:sub>analog) significantly prevented<jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>\u2010induced gastric lesions in the presence of indomethacin.<jats:styled-content style=\"fixed-case\">PGE<\/jats:styled-content><jats:sub>2<\/jats:sub>also reduced the severity of these lesions, and the effect was mimicked by the<jats:styled-content style=\"fixed-case\">EP<\/jats:styled-content>4 agonist,<jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>1\u2010329.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results suggest that endogenous<jats:styled-content style=\"fixed-case\">PGs<\/jats:styled-content>derived from<jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>\u20101 play a crucial role in gastric mucosal defense during<jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>, and this action is mainly mediated by<jats:styled-content style=\"fixed-case\">PGI<\/jats:styled-content><jats:sub>2<\/jats:sub>\/<jats:styled-content style=\"fixed-case\">IP<\/jats:styled-content>receptors and partly by<jats:styled-content style=\"fixed-case\">PGE<\/jats:styled-content><jats:sub>2<\/jats:sub>\/<jats:styled-content style=\"fixed-case\">EP<\/jats:styled-content>4 receptors.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.12767","type":"journal-article","created":{"date-parts":[[2014,12,21]],"date-time":"2014-12-21T17:13:10Z","timestamp":1419181990000},"page":"3-10","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Importance of cyclooxygenase\u20101\/prostacyclin in modulating gastric mucosal integrity under stress conditions"],"prefix":"10.1111","volume":"29","author":[{"given":"Kikuko","family":"Amagase","sequence":"first","affiliation":[{"name":"Division of Pathological Sciences Department of Pharmacology and Experimental Therapeutics Kyoto Pharmaceutical University Yamashina Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahoko","family":"Izumi","sequence":"additional","affiliation":[{"name":"Division of Pathological Sciences Department of Pharmacology and Experimental Therapeutics Kyoto Pharmaceutical University Yamashina Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Takahira","sequence":"additional","affiliation":[{"name":"Division of Pathological Sciences Department of Pharmacology and Experimental Therapeutics Kyoto Pharmaceutical University Yamashina Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Wada","sequence":"additional","affiliation":[{"name":"Division of Pathological Sciences Department of Pharmacology and Experimental Therapeutics Kyoto Pharmaceutical University Yamashina Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Division of Pathological Sciences Department of Pharmacology and Experimental Therapeutics Kyoto Pharmaceutical University Yamashina Kyoto Japan"},{"name":"General Incorporated Association Kyoto Research Center for Gastrointestinal Diseases Karasuma\u2010Oike Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,12,18]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2000.16510"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.300.3.754"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(90)90464-C"},{"key":"e_1_2_6_5_1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0022-3565(24)37564-0","article-title":"Effect of nitric oxide\u2010releasing aspirin on gastric functional and ulcerogenic responses in rats: comparison with aspirin","volume":"286","author":"Takeuchi K","year":"1998","journal-title":"J. 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