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Here, we demonstrate the efficacy of cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor (\n                    <jats:italic>R<\/jats:italic>\n                    )\u2010benzopyrimido\u2010pyrrolo\u2010oxazine\u2010dione\u201027 (BPO\u201027) in reducing bile acid\u2010induced fluid and electrolyte secretion in colon. Short\u2010circuit current measurements in human T84 colonic epithelial cells and planar colonic enteroid cultures showed a robust secretory response following mucosal but not serosal addition of chenodeoxycholic acid (CDCA) or its taurine conjugate, which was fully blocked by CFTR inhibitors, including (\n                    <jats:italic>R<\/jats:italic>\n                    )\u2010BPO\u201027. (\n                    <jats:italic>R<\/jats:italic>\n                    )\u2010BPO\u201027 also fully blocked CDCA\u2010induced secretory current in murine colon. CFTR activation by CDCA primarily involved Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling. In closed colonic loops\n                    <jats:italic>in vivo<\/jats:italic>\n                    , luminal CDCA produced a robust secretory response, which was reduced by ~70% by (\n                    <jats:italic>R<\/jats:italic>\n                    )\u2010BPO\u201027 or in CFTR\u2010deficient mice. In a rat model of BAD produced by intracolonic infusion of CDCA, (\n                    <jats:italic>R<\/jats:italic>\n                    )\u2010BPO\u201027 reduced the elevation in stool water content by &gt;55%. These results implicate CFTR activation in the colon as a major prosecretory mechanism of CDCA, a bile acid implicated in BAD, and support the potential therapeutic efficacy of CFTR inhibition in bile acid\u2010associated diarrheas.\u2014Duan, T., Cil, O., Tse, C. M., Sarker, R., Lin, R., Donowitz, M., Verkman, A. S. Inhibition of CFTR\u2010mediated intestinal chloride secretion as potential therapy for bile acid diarrhea. FASEB J. 33, 10924\u201310934 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201901166r","type":"journal-article","created":{"date-parts":[[2019,7,3]],"date-time":"2019-07-03T15:44:41Z","timestamp":1562168681000},"page":"10924-10934","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Inhibition of CFTR\u2010mediated intestinal chloride secretion as potential therapy for bile acid diarrhea"],"prefix":"10.1096","volume":"33","author":[{"given":"Tianying","family":"Duan","sequence":"first","affiliation":[{"name":"Department of Medicine University of California-San Francisco San Francisco California USA"},{"name":"Department of Physiology University of California-San Francisco San Francisco California USA"},{"name":"Department of Gastroenterology The Second Xiangya Hospital of Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onur","family":"Cil","sequence":"additional","affiliation":[{"name":"Department of Medicine University of California-San Francisco San Francisco California USA"},{"name":"Department of Pediatrics University of California-San Francisco San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Ming","family":"Tse","sequence":"additional","affiliation":[{"name":"Gastroenterology Division Department of Physiology Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafiquel","family":"Sarker","sequence":"additional","affiliation":[{"name":"Gastroenterology Division Department of Physiology Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruxian","family":"Lin","sequence":"additional","affiliation":[{"name":"Gastroenterology Division Department of Physiology Johns Hopkins University School of Medicine Baltimore Maryland USA"},{"name":"Department of Medicine Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Donowitz","sequence":"additional","affiliation":[{"name":"Gastroenterology Division Department of Physiology Johns Hopkins University School of Medicine Baltimore Maryland USA"},{"name":"Department of Medicine Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan S.","family":"Verkman","sequence":"additional","affiliation":[{"name":"Department of Medicine University of California-San Francisco San Francisco California USA"},{"name":"Department of Physiology University of California-San Francisco San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,7,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2009.04081.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2012.01953.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.5009\/gnl14397"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2012.05.006"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1586\/17474124.2014.851599"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/1756283X10377126"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2009.10.020"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM196908212810801"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2013-305088"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200318326"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00026.2001"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2015.111"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOG.0b013e3283358a45"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI106644"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01072128"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00416.2012"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00168.2016"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201600891R"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2003.11.005"},{"key":"e_1_2_8_21_1","doi-asserted-by":"crossref","first-page":"el26444","DOI":"10.1172\/jci.insight.126444","article-title":"Intestinal epithelial potassium channels and CFTR chloride channels activated in ErbB tyrosine kinase inhibitor diarrhea","volume":"4","author":"Duan T.","year":"2019","journal-title":"JCI Insight"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm200505e"},{"key":"e_1_2_8_23_1","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1021\/ml400069k","article-title":"Absolute configuration and biological properties of enantiomers of CFTR inhibitor BPO-27","volume":"4","author":"Snyder D. 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