{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:34:06Z","timestamp":1790836446293,"version":"4.1.0"},"reference-count":56,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,7,12]],"date-time":"2020-07-12T00:00:00Z","timestamp":1594512000000},"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"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The G protein\u2010coupled bile acid (BA) receptor, GPBA (previously named TGR5), mediates BA gastrointestinal (GI) activities. Our aim was to elucidate the mucosal and motility responses to selective GPBA agonists compared with conjugated BA (eg, taurodeoxycholate, TDCA) in mouse and human colon.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Ion transport responses to GPBA agonists or BAs were measured in mucosal preparations with intact submucous innervation, from C57Bl\/6, PYY\u2212\/\u2212, or GPBA\u2212\/\u2212 mice and compared with GPBA signaling in human colon. We also investigated the mechanisms underlying GPBA agonism in mucosae and on natural fecal pellet propulsion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>GPBA agonist Merck V stimulated basolateral responses involving peptide YY (PYY), cholinergic, and 5\u2010HT mechanisms in colonic mucosa. The PYY\u2010mediated GPBA signal was glucose\u2010sensitive. Luminal TDCA crossed the epithelial lining via the apical sodium\u2010dependent BA transporter (ASBT) and its inhibitor, GSK2330672 significantly reduced luminal, but not basolateral TDCA activity. Merck V also slowed natural fecal pellet progression in wild\u2010type and PYY\u2212\/\u2212 colons but not in GPBA\u2212\/\u2212 colon, while TDCA increased motility in wild\u2010type colon. The antimotile GPBA effect was reversed by blockade of glucagon\u2010like peptide 1 (GLP\u20101) receptors or nitric oxide synthase, indicating involvement of GLP\u20101 and nitric oxide.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>We conclude that several different targets within the lamina propria express GPBA, including L cells (that release PYY and GLP\u20101), enterochromaffin cells and neurons (that release 5\u2010HT), and other enteric neurons. Furthermore, luminal\u2010conjugated BAs require transport across the epithelium via ASBT in order to activate basolateral GPBA.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13943","type":"journal-article","created":{"date-parts":[[2020,7,13]],"date-time":"2020-07-13T02:09:30Z","timestamp":1594606170000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Synthetic G protein\u2010coupled bile acid receptor agonists and bile acids act via basolateral receptors in ileal and colonic mucosa"],"prefix":"10.1111","volume":"32","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 and Neuroscience London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thue 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