{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T01:46:40Z","timestamp":1788918400083,"version":"build-2803163510"},"reference-count":55,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2015,4,30]],"date-time":"2015-04-30T00:00:00Z","timestamp":1430352000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK57061"],"award-info":[{"award-number":["DK57061"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Menarini Ricerche"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Otilonium bromide (<jats:styled-content style=\"fixed-case\">OB<\/jats:styled-content>) is used as a spasmolytic drug in the treatment of the functional bowel disorder irritable bowel syndrome. Although its acute effects on colonic relaxation are well\u2010characterized, little is known about the effects of chronic administration of<jats:styled-content style=\"fixed-case\">OB<\/jats:styled-content>on enteric neurons, neuromuscular transmission, and interstitial cells of Cajal (<jats:styled-content style=\"fixed-case\">ICC<\/jats:styled-content>), key regulators of the gut function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adult Sprague\u2013Dawley rats were treated with<jats:styled-content style=\"fixed-case\">OB<\/jats:styled-content>in drinking water at a dose of 2\u00a0mg\/kg for 30\u00a0days. The colons of<jats:styled-content style=\"fixed-case\">OB<\/jats:styled-content>\u2010treated and age\u2010matched control rats were studied by confocal immunohistochemistry to detect immunoreactivity (<jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>) in myenteric plexus neurons for nitrergic and tachykininergic markers, and also by microelectrode electrophysiology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Using immunohistochemistry, chronic<jats:styled-content style=\"fixed-case\">OB<\/jats:styled-content>administration did not change total neuron number, assessed by anti\u2010Hu<jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>, but resulted in a significant increase in<jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content>1 receptor positive neurons, a decrease in neuronal nitric oxide synthase expressing neurons, and a reduction in volume of substance P in nerve fibers in the myenteric plexus. Chronic<jats:styled-content style=\"fixed-case\">OB<\/jats:styled-content>administration potentiated inhibitory and excitatory junction potentials evoked by repetitive electrical field stimulation. The various types of colonic<jats:styled-content style=\"fixed-case\">ICC<\/jats:styled-content>, detected by Kit<jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>, were not altered nor were slow waves or smooth muscle membrane potential.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>Chronic treatment with<jats:styled-content style=\"fixed-case\">OB<\/jats:styled-content>caused significant changes in the nitrergic and tachykinergic components of the myenteric plexus and in both inhibitory and excitatory neurotransmission in the rat colon.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.12576","type":"journal-article","created":{"date-parts":[[2015,4,30]],"date-time":"2015-04-30T09:43:12Z","timestamp":1430386992000},"page":"997-1009","source":"Crossref","is-referenced-by-count":8,"title":["Changes in nitrergic and tachykininergic pathways in rat proximal colon in response to chronic treatment with otilonium bromide"],"prefix":"10.1111","volume":"27","author":[{"given":"G.","family":"Cipriani","sequence":"first","affiliation":[{"name":"Enteric NeuroScience Program Division of Gastroenterology and Hepatology Mayo Clinic Rochester Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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