{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T01:46:41Z","timestamp":1788918401520,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2013,7,31]],"date-time":"2013-07-31T00:00:00Z","timestamp":1375228800000},"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":[[2013,11]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Otilonium bromide (OB<\/jats:styled-content>) is a quaternary ammonium derivative used for the treatment of intestinal hypermotility and is endowed with neurokinin2 receptor (NK<\/jats:styled-content>2r) antagonist and Ca2+<\/jats:sup>channel blocker properties. Therefore, the possibility that OB<\/jats:styled-content> might play a role in the neurokinin receptor\/Substance\u2010P\/nitric oxide (NK<\/jats:styled-content>r\/SP<\/jats:styled-content>\/NO<\/jats:styled-content>) circuit was investigated after chronic exposition to the drug.<\/jats:p><\/jats:sec>Methods<\/jats:title>Rats were treated with OB<\/jats:styled-content> 2\u201320\u00a0mg\u00a0kg\u22121<\/jats:sup> for 10 and 30\u00a0days. In the proximal colon, the expression and distribution of muscle NO<\/jats:styled-content>synthase 1 (NOS<\/jats:styled-content>1), NK<\/jats:styled-content>1r, NK<\/jats:styled-content>2r, SP<\/jats:styled-content> and Cav<\/jats:sub> 1.2 subunit (for L\u2010type Ca2+<\/jats:sup>channel) and the spontaneous activity and stimulated responses to NK<\/jats:styled-content>1r and NK<\/jats:styled-content>2r agonists were investigated.<\/jats:p><\/jats:sec>Key Results<\/jats:title>Immunohistochemistry showed a redistribution of NK<\/jats:styled-content>1r and L\u2010type Ca2+<\/jats:sup>channel in muscle cells with no change of NK<\/jats:styled-content>2r at 30\u00a0days, a significant increase in muscle NOS<\/jats:styled-content>1 expression at 10\u00a0days and a significant decrease in the SP<\/jats:styled-content> content early in the ganglia and later in the intramuscular nerve fibers. Functional studies showed no change in spontaneous activity but a significant increase in maximal contraction induced by NK<\/jats:styled-content>1r agonist.<\/jats:p><\/jats:sec>Conclusions & Inferences<\/jats:title>Chronic exposition to OB<\/jats:styled-content> significantly affects the NK<\/jats:styled-content>r\/SP<\/jats:styled-content>\/NO<\/jats:styled-content> circuit. The progressive decrease in SP<\/jats:styled-content>\u2010expression might be the consequence of the persistent presence of OB<\/jats:styled-content>, the increase of NOS<\/jats:styled-content>1 expression in muscle cells at 10\u00a0days in an attempt to guarantee an adequate NO<\/jats:styled-content> production, and, at 30\u00a0days, the redistribution of the L\u2010type Ca2+<\/jats:sup>channel and NK<\/jats:styled-content>1r as a sign to compensate the drug channel block by re\u2010cycling both of them. The physiological data suggest NK<\/jats:styled-content>1r hypersensitivity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.12197","type":"journal-article","created":{"date-parts":[[2013,8,1]],"date-time":"2013-08-01T02:08:59Z","timestamp":1375322939000},"source":"Crossref","is-referenced-by-count":9,"title":["Chronic treatment with otilonium bromide induces changes in L\u2010type Ca<\/scp><\/scp>2+<\/sup>channel, tachykinins, and nitric oxide synthase expression in rat colon muscle coat"],"prefix":"10.1111","volume":"25","author":[{"given":"C.","family":"Traini","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Medicine Section of Anatomy and Histology University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Cipriani","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine Section of Anatomy and Histology University of Florence Florence 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