{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T07:31:26Z","timestamp":1789457486586,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,7,17]],"date-time":"2017-07-17T00:00:00Z","timestamp":1500249600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DK54221"],"award-info":[{"award-number":["R01 DK54221"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Short\u2010chain fatty acids (<jats:styled-content style=\"fixed-case\">SCFA<\/jats:styled-content>) are microbial fermentation products absorbed by the colon. We recently reported that activation of the<jats:styled-content style=\"fixed-case\">SCFA<\/jats:styled-content>receptor termed free fatty acid receptor 3 (<jats:styled-content style=\"fixed-case\">FFA<\/jats:styled-content>3), expressed on cholinergic nerves, suppresses nicotinic acetylcholine receptor (<jats:styled-content style=\"fixed-case\">nAChR<\/jats:styled-content>)\u2010mediated transepithelial anion secretion. This study aimed to clarify how activation of neurally expressed<jats:styled-content style=\"fixed-case\">FFA<\/jats:styled-content>3 affects colonic motor function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">FFA<\/jats:styled-content>3\u2010expressing myenteric neurons were identified by immunostaining; contractions of isolated circular muscle strips obtained from rat proximal colon were measured by isometric transducers. The effect of<jats:styled-content style=\"fixed-case\">FFA<\/jats:styled-content>3 agonists on defecation<jats:italic>in vivo<\/jats:italic>was examined in an exogenous serotonin\u2010induced defecation model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">FFA<\/jats:styled-content>3 immunoreactivity was located in nitrergic and cholinergic neurons in the myenteric plexus. In isolated circular muscle strips without mucosa and submucosa, the addition of nicotine (10\u00a0\u03bcM) or serotonin transiently relaxed the muscle through nitrergic neurons, whereas high concentrations of nicotine (100\u00a0\u03bcM) induced large\u2010amplitude contractions that were mediated by cholinergic neurons. Pretreatment with<jats:styled-content style=\"fixed-case\">FFA<\/jats:styled-content>3 agonists inhibited nicotine\u2010 or serotonin\u2010induced motility changes but had no effect on bethanechol\u2010induced direct muscle contractions. The G<jats:sub>i\/o<\/jats:sub>inhibitor pertussis toxin reversed the inhibitory effect of an<jats:styled-content style=\"fixed-case\">FFA<\/jats:styled-content>3 agonist<jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>420626 on nicotine\u2010evoked contractions, suggesting that<jats:styled-content style=\"fixed-case\">FFA<\/jats:styled-content>3 activation suppresses<jats:styled-content style=\"fixed-case\">nAChR<\/jats:styled-content>\u2010mediated neural activity in myenteric neurons, consistent with an<jats:styled-content style=\"fixed-case\">FFA<\/jats:styled-content>3\u2010mediated antisecretory effect. In conscious rats, exogenous serotonin increased the volume of fecal output, compared with the vehicle\u2010 or<jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>420626\u2010treated groups. Pretreatment with<jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>420626 significantly suppressed serotonin\u2010induced fecal output.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Inferences<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">FFA<\/jats:styled-content>3 is a promising target for the treatment of neurogenic diarrheal disorders by suppressing<jats:styled-content style=\"fixed-case\">nAChR<\/jats:styled-content>\u2010mediated neural pathways.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13157","type":"journal-article","created":{"date-parts":[[2017,7,17]],"date-time":"2017-07-17T07:06:38Z","timestamp":1500275198000},"source":"Crossref","is-referenced-by-count":44,"title":["Free fatty acid receptor 3 activation suppresses neurogenic motility in rat proximal colon"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5395-0497","authenticated-orcid":false,"given":"I.","family":"Kaji","sequence":"first","affiliation":[{"name":"Department of Medicine University of California Los Angeles Los Angeles CA USA"},{"name":"Greater Los Angeles VA Healthcare System Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Akiba","sequence":"additional","affiliation":[{"name":"Department of Medicine University of California Los Angeles Los Angeles CA USA"},{"name":"Greater Los Angeles VA Healthcare System Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Furuyama","sequence":"additional","affiliation":[{"name":"Neuroethology &amp; Bioengineering Graduate School of Life &amp; Medical Sciences Doshisha University Kyoto Japan"},{"name":"Japan Society for the Promotion of Science Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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