{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T02:54:31Z","timestamp":1788317671557,"version":"build-2803163510"},"reference-count":52,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T00:00:00Z","timestamp":1680480000000},"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","id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Enterochromaffin (EC) cell\u2010derived 5\u2010hydroxytryptamine (5\u2010HT) is a mediator of toxin\u2010induced reflexes, initiating emesis via vagal and central 5\u2010HT\n                      <jats:sub>3<\/jats:sub>\n                      receptors. The amine is also involved in gastrointestinal (GI) reflexes that are prosecretory and promotile, and recently 5\u2010HT's roles in chemosensation in the distal bowel have been described. We set out to establish the efficacy of 5\u2010HT signaling, local 5\u2010HT levels and pharmacology in discrete regions of the mouse small and large intestine. We also investigated the inter\u2010relationships between incretin hormones, glucagon\u2010like peptide\u20101 (GLP\u20101) and gastric inhibitory polypeptide (GIP) and endogenous 5\u2010HT in mucosal and motility assays.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Adult mouse GI mucosae were mounted in Ussing chambers and area\u2010specific studies were performed to establish the 5\u2010HT\n                      <jats:sub>3<\/jats:sub>\n                      and 5\u2010HT\n                      <jats:sub>4<\/jats:sub>\n                      pharmacology, the sidedness of responses, and the inter\u2010relationships between incretins and endogenous 5\u2010HT. Natural fecal pellet transit in vitro and full\u2010length GI transit in vivo were also measured.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      We observed the greatest level of tonic and exogenous 5\u2010HT\u2010induced ion transport and highest levels of 5\u2010HT in ascending colon mucosa. Here both 5\u2010HT\n                      <jats:sub>3<\/jats:sub>\n                      and 5\u2010HT\n                      <jats:sub>4<\/jats:sub>\n                      receptors were involved but elsewhere in the GI tract epithelial basolateral 5\u2010HT\n                      <jats:sub>4<\/jats:sub>\n                      receptors mediate 5\u2010HT's prosecretory effect. Exendin\u20104 and GIP induced 5\u2010HT release in the ascending colon, while L cell\u2010derived PYY also contributed to GIP mucosal effects in the descending colon. Both peptides slowed colonic transit.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions &amp; Inferences<\/jats:title>\n                    <jats:p>\n                      We provide functional evidence for paracrine interplay between 5\u2010HT, GLP\u20101 and GIP, particularly in the colonic mucosal region. Basolateral epithelial 5\u2010HT\n                      <jats:sub>4<\/jats:sub>\n                      receptors mediated both 5\u2010HT and incretin mucosal responses in healthy colon.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nmo.14589","type":"journal-article","created":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T11:30:37Z","timestamp":1680521437000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Paracrine relationship between incretin hormones and endogenous 5\u2010hydroxytryptamine in the small and large intestine"],"prefix":"10.1111","volume":"35","author":[{"given":"Iain R.","family":"Tough","sequence":"first","affiliation":[{"name":"Wolfson Centre for Age\u2010Related Diseases, Institute of Psychology, Psychiatry and Neuroscience King's College London  Hodgkin Building, Guy's Campus London SE1 1UL 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Denmark"}],"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":"Wolfson Centre for Age\u2010Related Diseases, Institute of Psychology, Psychiatry and Neuroscience King's College London  Hodgkin Building, Guy's Campus London SE1 1UL 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