{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T02:10:09Z","timestamp":1747188609894,"version":"3.40.5"},"reference-count":47,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,1,25]],"date-time":"2019-01-25T00:00:00Z","timestamp":1548374400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK088892","DK108755"],"award-info":[{"award-number":["DK088892","DK108755"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:sec><jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p>\n<jats:p>The tracer <jats:sup>36<\/jats:sup>Cl<jats:sup>\u2212<\/jats:sup>, currently used to measure transepithelial Cl<jats:sup>\u2212<\/jats:sup> fluxes, has become prohibitively expensive, threatening its future use. <jats:sup>125<\/jats:sup>Iodide, previously validated alongside <jats:sup>36<\/jats:sup>Cl<jats:sup>\u2212<\/jats:sup> as a tracer of Cl<jats:sup>\u2212<\/jats:sup> efflux by cells, has not been tested as a surrogate for <jats:sup>36<\/jats:sup>Cl<jats:sup>\u2212<\/jats:sup> across epithelia.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item><jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p>\n<jats:p>We demonstrate that <jats:sup>125<\/jats:sup>I<jats:sup>\u2212<\/jats:sup> can serve as an inexpensive replacement for measuring Cl<jats:sup>\u2212<\/jats:sup> transport across mouse large intestine, tracking Cl<jats:sup>\u2212<\/jats:sup> transport in response to cAMP stimulation (inducing Cl<jats:sup>\u2212<\/jats:sup> secretion) in the presence and absence of the main gastrointestinal Cl<jats:sup>\u2212<\/jats:sup>\u2013HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> exchanger, DRA.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Chloride transport is important for driving fluid secretion and absorption by the large intestine, with dysregulation resulting in diarrhoea\u2010associated pathologies. The radioisotope <jats:sup>36<\/jats:sup>Cl<jats:sup>\u2212<\/jats:sup> has long been used as a tracer to measure epithelial Cl<jats:sup>\u2212<\/jats:sup> transport but is prohibitively expensive. <jats:sup>125<\/jats:sup>Iodide has been used as an alternative to <jats:sup>36<\/jats:sup>Cl<jats:sup>\u2212<\/jats:sup> in some transport assays but has never been validated as an alternative for tracing bidirectional transepithelial Cl<jats:sup>\u2212<\/jats:sup> fluxes. The goal of this study was to validate <jats:sup>125<\/jats:sup>I<jats:sup>\u2212<\/jats:sup> as an alternative to <jats:sup>36<\/jats:sup>Cl<jats:sup>\u2212<\/jats:sup> for measurement of Cl<jats:sup>\u2212<\/jats:sup> transport by the intestine. Simultaneous fluxes of <jats:sup>36<\/jats:sup>Cl<jats:sup>\u2212<\/jats:sup> and <jats:sup>125<\/jats:sup>I<jats:sup>\u2212<\/jats:sup> were measured across the mouse caecum and distal colon. Net Cl<jats:sup>\u2212<\/jats:sup> secretion was induced by the stimulation of cAMP with a cocktail of forskolin (FSK) and 3\u2010isobutyl\u20101\u2010methylxanthine (IBMX). Unidirectional fluxes of <jats:sup>125<\/jats:sup>I<jats:sup>\u2212<\/jats:sup> correlated well with <jats:sup>36<\/jats:sup>Cl<jats:sup>\u2212<\/jats:sup> fluxes after cAMP\u2010induced net Cl<jats:sup>\u2212<\/jats:sup> secretion, occurring predominantly through a reduction in the absorptive mucosal\u2010to\u2010serosal Cl<jats:sup>\u2212<\/jats:sup> flux rather than by stimulation of the secretory serosal\u2010to\u2010mucosal Cl<jats:sup>\u2212<\/jats:sup> flux. Correlations between <jats:sup>125<\/jats:sup>I<jats:sup>\u2212<\/jats:sup> fluxes and <jats:sup>36<\/jats:sup>Cl<jats:sup>\u2212<\/jats:sup> fluxes were maintained in epithelia from mice lacking DRA (Slc26a3), the main Cl<jats:sup>\u2212<\/jats:sup>\u2013HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> exchanger responsible for Cl<jats:sup>\u2212<\/jats:sup> absorption by the large intestine. Lower rates of Cl<jats:sup>\u2212<\/jats:sup> and I<jats:sup>\u2212<\/jats:sup> absorption in the DRA knockout intestine suggest that DRA might have a previously unrecognized role in iodide uptake. This study validates that <jats:sup>125<\/jats:sup>I<jats:sup>\u2212<\/jats:sup> traces transepithelial Cl<jats:sup>\u2212<\/jats:sup> fluxes across the mouse large intestine, provides insights into the mechanism of net Cl<jats:sup>\u2212<\/jats:sup> secretion and suggests that DRA might be involved in intestinal iodide absorption.<\/jats:p><\/jats:sec>","DOI":"10.1113\/ep087445","type":"journal-article","created":{"date-parts":[[2019,1,8]],"date-time":"2019-01-08T21:32:53Z","timestamp":1546983173000},"page":"334-344","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["<sup>125<\/sup>Iodide as a surrogate tracer for epithelial chloride transport by the mouse large intestine <i>in vitro<\/i>"],"prefix":"10.1113","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2391-5153","authenticated-orcid":false,"given":"Christine E.","family":"Stephens","sequence":"first","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine College of Medicine University of Florida  Gainesville FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan M.","family":"Whittamore","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine College of Medicine University of Florida  Gainesville FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marguerite","family":"Hatch","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine College of Medicine University of Florida  Gainesville FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,1,25]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00366.2010"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.2001.280.4.G603"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00512476"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/tox.20271"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1990.259.1.F111"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.90649.2008"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.43.6.1137"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1999.79.1.S47"},{"key":"e_1_2_8_10_1","first-page":"477","article-title":"Coexistance of absorptive and secretory NaCl processes in the isolated lizard colon: Effects of cyclic AMP","volume":"8","author":"D\u00edaz M.","year":"1991","journal-title":"Zoological Science"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr0701761"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.43.27230"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplegacy.1971.221.4.992"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.38.26946"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00167.2013"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-97-2-307"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M403779200"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00297.2001"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP270818"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00107.2015"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00374396"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00374677"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1998.274.2.F275"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.90581.2008"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00041.2016"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00194.2014"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2004.05.026"},{"key":"e_1_2_8_28_1","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1242\/jeb.203.13.1947","article-title":"Permeation through the CFTR chloride channel","volume":"203","author":"McCarty N. 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