{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T20:11:21Z","timestamp":1790107881110,"version":"4.0.1"},"reference-count":50,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,8,23]],"date-time":"2018-08-23T00:00:00Z","timestamp":1534982400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/N006763\/1"],"award-info":[{"award-number":["BB\/N006763\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007872","name":"Bowel and Cancer Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007872","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Propionate exhibits affinity for free fatty acid receptor 2 (FFA2, formerly GPR43) and FFA3 (GPR41). These two G protein\u2010coupled receptors (GPCRs) are expressed by enteroendocrine L cells that contain anorectic peptide YY (PYY) and glucagon\u2010like peptide 1 (GLP\u20101), while FFA3 is also expressed by enteric neurons. Few studies have investigated the individual roles of FFA2 and FFA3 in propionate's gastrointestinal (GI) effects. Here, we compared FFA2, FFA3, and propionate mucosal responses utilizing selective ligands including an FFA3 antagonist, in mouse and human colonic mucosa.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Vectorial ion transport was measured in native colonic preparations from normal mouse and human colon with intact submucosal innervation. Endogenous fecal pellet propulsion was monitored in colons isolated from wild\u2010type (WT) and PYY\u2212\/\u2212 mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>FFA2 and FFA3 signaling differed significantly. FFA2 agonism involved endogenous L cell\u2010derived PYY and was glucose dependent, while FFA3 agonism was independent of PYY and glucose, but required submucosal enteric neurons for activity. Tonic FFA3 activity was observed in mouse and human colon mucosa. Apical propionate responses were a combination of FFA2\u2010PYY mediation and FFA3 neuronal GLP\u20101\u2010 and CGRP\u2010dependent signaling in mouse ascending colon mucosa. Propionate also slowed WT and PYY\u2212\/\u2212 colonic transit, and this effect was blocked by a GLP\u20101 receptor antagonist.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>We conclude that luminal propionate costimulates FFA2 and FFA3 pathways, reducing anion secretion and slowing colonic motility; FFA2 via PYY mediation and FFA3 signaling by activation of enteric sensory neurons.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13454","type":"journal-article","created":{"date-parts":[[2018,8,23]],"date-time":"2018-08-23T08:53:14Z","timestamp":1535014394000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Signaling of free fatty acid receptors 2 and 3 differs in colonic mucosa following selective agonism or coagonism by luminal propionate"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4829-9369","authenticated-orcid":false,"given":"Iain R.","family":"Tough","sequence":"first","affiliation":[{"name":"King's College London Wolfson Centre for Age\u2010Related Diseases, Institute of Psychiatry, Psychology &amp; Neuroscience London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Forbes","sequence":"additional","affiliation":[{"name":"King's College London Wolfson Centre for Age\u2010Related Diseases, Institute of Psychiatry, Psychology &amp; Neuroscience London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9024-1497","authenticated-orcid":false,"given":"Helen M.","family":"Cox","sequence":"additional","affiliation":[{"name":"King's College London Wolfson Centre for Age\u2010Related Diseases, Institute of Psychiatry, Psychology &amp; Neuroscience London 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