{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T11:10:07Z","timestamp":1774437007462,"version":"3.50.1"},"reference-count":53,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,3,13]],"date-time":"2015-03-13T00:00:00Z","timestamp":1426204800000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Ferring Research Institute"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["DK-R01DK091281"],"award-info":[{"award-number":["DK-R01DK091281"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Linaclotide, a synthetic guanylyl cyclase C (<jats:styled-content style=\"fixed-case\">GC<\/jats:styled-content>\u2010C) agonist, and the prostone analog, Lubiprostone, are approved to manage chronic idiopathic constipation and constipation\u2010predominant irritable bowel syndrome. Lubiprostone also protects intestinal mucosal barrier function in ischemia.<jats:styled-content style=\"fixed-case\">GC<\/jats:styled-content>\u2010C signaling regulates local fluid balance and other components of intestinal mucosal homeostasis including epithelial barrier function. The aim of this study was to compare if select dosing regimens differentially affect linaclotide and lubiprostone modulation of ion transport and barrier properties of normal human colonic mucosa. Normal sigmoid colon biopsies from healthy subjects were mounted in Ussing chambers. Tissues were treated with linaclotide, lubiprostone, or vehicle to determine effects on short\u2010circuit current (<jats:italic>I<\/jats:italic><jats:sub>sc<\/jats:sub>). Subsequent<jats:italic>I<\/jats:italic><jats:sub>sc<\/jats:sub>responses to the<jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content>agonist, forskolin, and the calcium agonist, carbachol, were also measured to assess if either drug caused desensitization. Barrier properties were assessed by measuring transepithelial electrical resistance.<jats:italic>I<\/jats:italic><jats:sub>sc<\/jats:sub>responses to linaclotide and lubiprostone were significantly higher than vehicle control when administered bilaterally or to the mucosal side only. Single versus cumulative concentrations of linaclotide showed differences in efficacy while cumulative but not single dosing caused desensitization to forskolin. Lubiprostone reduced forskolin responses under all conditions. Linaclotide and lubiprostone exerted a positive effect on<jats:styled-content style=\"fixed-case\">TER<\/jats:styled-content>that was dependent on the dosing regimen. Linaclotide and lubiprostone increase ion transport responses across normal human colon but linaclotide displays increased sensitivity to the dosing regimen used. These findings may have implications for dosing protocols of these agents in patients with constipation.<\/jats:p>","DOI":"10.1002\/prp2.128","type":"journal-article","created":{"date-parts":[[2015,3,13]],"date-time":"2015-03-13T11:40:23Z","timestamp":1426246823000},"source":"Crossref","is-referenced-by-count":6,"title":["A comparison of linaclotide and lubiprostone dosing regimens on ion transport responses in human colonic mucosa"],"prefix":"10.1002","volume":"3","author":[{"given":"Sang Bum","family":"Kang","sequence":"first","affiliation":[{"name":"Division of Gastroenterology Department of Internal Medicine St. Mary's Hospital Catholic University of Korea Seoul Korea"},{"name":"Division of Gastroenterology School of Medicine University of California, San Diego La Jolla California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald R.","family":"Marchelletta","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology School of Medicine University of California, San Diego La Jolla California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harrison","family":"Penrose","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology School of Medicine University of California, San Diego La Jolla California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Docherty","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology School of Medicine University of California, San Diego La Jolla California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Declan F.","family":"McCole","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences School of Medicine University of California, Riverside Riverside California"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,3,13]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-010-1495-8"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00366.2007"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-009-1068-x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.62.1.535"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjp.2008.84"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.05.037"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1586\/17474124.2013.820045"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.112.199430"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.01.010"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1994.tb06355.x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2012.254"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.90649.2008"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.257.5073.1125"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00528.2003"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M312567200"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2210-12-3"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12013-012-9406-6"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00077.2014"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702290"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112311"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.90447.2008"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.75.6.2800"},{"key":"e_1_2_9_24_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1128\/iai.24.1.19-23.1979","article-title":"Effect of purified escherichia coli heat\u2010stable enterotoxin on intestinal cyclic nucleotide metabolism and fluid secretion","volume":"24","author":"Giannella RA","year":"1979","journal-title":"Infect Immun"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.4.8.1091"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2000.279.6.C1787"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0016139"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.1988.tb08462.x"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2008.03629.x"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2007.01524.x"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2008.59"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.12604"},{"issue":"2","key":"e_1_2_9_33_1","first-page":"G394","article-title":"Peptide\u2010regulated guanylate cyclase pathways in rat colon: in situ localization of GCA, GCC, and Guanylin mRNA","volume":"265","author":"Li Z","year":"1993","journal-title":"Am J Physiol"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0031686"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200318743"},{"key":"e_1_2_9_36_1","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/S0031-6997(24)01457-1","article-title":"Guanylyl cyclases and signaling by cyclic GMP","volume":"52","author":"Lucas KA","year":"2000","journal-title":"Pharmacol Rev"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707175"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1998.275.6.G1274"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.140.11.5022"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gastro.2005.06.004"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.2165\/11470590-000000000-00000"},{"key":"e_1_2_9_42_1","first-page":"1248","article-title":"The positive inotropic\u2010acting forskolin, a potent adenylate cyclase activator","volume":"31","author":"Metzger H","year":"1981","journal-title":"Arzneimittelforschung"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.06.004"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00183.2006"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.14.6012"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00072.2011"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02525"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100325"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(97)85404-0"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-011-1702-2"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1996.1286"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.1997.v112.pm9024297"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(00)70419-7"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.2741\/1687"}],"container-title":["Pharmacology Research &amp; Perspectives"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fprp2.128","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fprp2.128","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.128","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/prp2.128","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.128","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T23:27:27Z","timestamp":1747783647000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/prp2.128"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3]]},"references-count":53,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2015,3]]}},"alternative-id":["10.1002\/prp2.128"],"URL":"https:\/\/doi.org\/10.1002\/prp2.128","archive":["Portico"],"relation":{},"ISSN":["2052-1707","2052-1707"],"issn-type":[{"value":"2052-1707","type":"print"},{"value":"2052-1707","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3]]},"article-number":"e00128"}}