{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T04:24:38Z","timestamp":1771561478486,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,7,11]],"date-time":"2017-07-11T00:00:00Z","timestamp":1499731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"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":[],"crossmark-restriction":false},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2018,1]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Glucagon\u2010like peptide (GLP<\/jats:styled-content>)\u20101 is an incretin hormone and its mimetics are proven antidiabetic and antiobesity drugs. GLP<\/jats:styled-content>\u20101 exerts antimotility and mucosal proliferative activities but its epithelial ion transport effects are uncharacterized and these may contribute to the gastrointestinal (GI<\/jats:styled-content>) disturbance, i.e., diarrhea experienced with some GLP<\/jats:styled-content>\u20101 mimetics. Our aim was to establish GLP<\/jats:styled-content>\u20101 agonist mechanisms and identify potential mucosal mediator(s) in the colonic tissue from C57BL\/6J mice.<\/jats:p><\/jats:sec>Methods<\/jats:title>A tissue survey of GLP<\/jats:styled-content>\u20101 responses (using exendin 4, Ex4) and \u03b1\u2010calcitonin gene\u2010related peptide (\u03b1CGRP<\/jats:styled-content>) was undertaken, dividing the mouse colon into eight adjacent mucosal\u2010submucosal preparations. Each preparation was voltage\u2010clamped and changes in short\u2010circuit current (Isc) measured. The involvement of submucosal neurons in GLP<\/jats:styled-content>\u20101 agonism was tested using Ex(9\u201039) and tetrodotoxin (TTX<\/jats:styled-content>), and CGRP<\/jats:styled-content> receptors were blocked with BIBN<\/jats:styled-content>4094.<\/jats:p><\/jats:sec>Key Results<\/jats:title>Ex4 responses along the length of the colon were inhibited by the GLP<\/jats:styled-content>\u20101 antagonist, Ex(9\u201039) or TTX<\/jats:styled-content>, indicating neural mediation in all colonic regions. In the ascending colon, Ex4 increased Isc levels that were abolished by 10\u00a0nM BIBN<\/jats:styled-content>4096, while in the descending colon it reduced Isc levels that were again BIBN<\/jats:styled-content>4096\u2010sensitive, but at 1\u00a0\u03bcM. The latter \u03b1CGRP<\/jats:styled-content> response was dependent on epithelial Cl\u2212<\/jats:sup> conductance and Na+<\/jats:sup>\/K+<\/jats:sup>\u2010ATP<\/jats:styled-content>ase, and was partially (~25%) peptide YY<\/jats:styled-content>\u2010mediated, but was not nitrergic, somatostatin sst2<\/jats:sub>, or \u03b12<\/jats:sub>\u2010adrenoceptor\u2010mediated.<\/jats:p><\/jats:sec>Conclusions and Inferences<\/jats:title>GLP<\/jats:styled-content>\u20101 modulates epithelial ion transport indirectly by activating CGRP<\/jats:styled-content>\u2010containing submucosal enteric neurons in the mouse colon. This GLP<\/jats:styled-content>\u20101\u2010CGRP<\/jats:styled-content> response was area\u2010specific and could potentially contribute to the diarrheal side effect of certain GLP<\/jats:styled-content>\u20101R therapeutics.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13149","type":"journal-article","created":{"date-parts":[[2017,7,11]],"date-time":"2017-07-11T07:02:41Z","timestamp":1499756561000},"source":"Crossref","is-referenced-by-count":12,"title":["Mucosal glucagon\u2010like peptide 1 (GLP<\/scp>\u20101) responses are mediated by calcitonin gene\u2010related peptide (CGRP<\/scp>) in the mouse colon and both peptide responses are area\u2010specific"],"prefix":"10.1111","volume":"30","author":[{"given":"I.R.","family":"Tough","sequence":"first","affiliation":[{"name":"Wolfson Centre for Age\u2010Related Diseases King's College London IoPPN Guy's Campus London 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