{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T17:46:00Z","timestamp":1774892760268,"version":"3.50.1"},"reference-count":38,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2014,7,13]],"date-time":"2014-07-13T00:00:00Z","timestamp":1405209600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Although opioids induce intestinal muscle contraction and provoke constipation, the intestinal region(s) that contribute to the constipation have remained unclear. We report here a region\u2010specific response of intestinal muscle contraction to morphine and its correlation with<jats:italic>in vivo<\/jats:italic>constipation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Regions of mice small and large intestines were dissected histologically and circular muscle contractile responses were measured using isometric transducers. Bead expulsion assays were performed to assess<jats:italic>in vivo<\/jats:italic>constipation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>The strongest contraction in response to morphine was detected in the rectum. The distal and transverse colon also showed strong contractions, whereas weak responses were detected in the proximal colon, jejunum, and ileum. Regarding the sustainability of muscle contractions during morphine exposure, prolonged waves were detected only in the rectum, while the waves diminished gradually in other regions. To identify the mechanism(s) underlying this difference, we focused on nitric oxide synthase (<jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content>). In the distal colon, decreased contraction during morphine exposure was recovered by application of a<jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content>inhibitor (L\u2010<jats:styled-content style=\"fixed-case\">NAME<\/jats:styled-content>), while a<jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content>substrate (L\u2010arginine) enhanced contractile degradation. In contrast L\u2010<jats:styled-content style=\"fixed-case\">NAME<\/jats:styled-content>and L\u2010arginine modestly affected the sustained contraction in the rectum. To confirm the correlation with constipation, beads were inserted into the transverse colon, distal colon, or rectum after morphine administration and expulsion times were examined. Beads tended to stop at the rectum even when inserted in the deeper colonic regions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>The rectum showed the greatest response to morphine in both<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>analyses, therefore it may play a key role for opioid\u2010induced constipation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.12387","type":"journal-article","created":{"date-parts":[[2014,7,15]],"date-time":"2014-07-15T15:57:33Z","timestamp":1405439853000},"page":"1396-1407","source":"Crossref","is-referenced-by-count":32,"title":["Circular muscle contraction in the mice rectum plays a key role in morphine\u2010induced constipation"],"prefix":"10.1111","volume":"26","author":[{"given":"H.","family":"Ono","sequence":"first","affiliation":[{"name":"Pain &amp; Neurology Medicinal Research Laboratories Shionogi and Co., Ltd. Toyonaka Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Pain &amp; Neurology Medicinal Research Laboratories Shionogi and Co., Ltd. Toyonaka Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology Josai International University Togane Chiba Japan"},{"name":"Division of Pathological Sciences Department of Pharmacology and Experimental Therapeutics Kyoto Pharmaceutical University Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Horie","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology Josai International University Togane Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Sakaguchi","sequence":"additional","affiliation":[{"name":"Pain &amp; Neurology Medicinal Research Laboratories Shionogi and Co., Ltd. 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