{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T08:01:59Z","timestamp":1790928119438,"version":"4.1.0"},"reference-count":58,"publisher":"American Physiological Society","issue":"1","funder":[{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)","doi-asserted-by":"publisher","award":["R01DK103759"],"award-info":[{"award-number":["R01DK103759"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2019,1,1]]},"abstract":"<jats:p>\n                    The irritable bowel syndrome (IBS) is a functional gastrointestinal motor and visceral sensation disorder that is more common in women than men. Female serotonin transporter (SERT)-gene knockout (KO) rats exhibit hypersensitivity to colorectal balloon distention (CRD) that mimics colonic hypersensitivity occurring in female IBS patients. Alosetron (5-HT\n                    <jats:sub>3<\/jats:sub>\n                    receptor antagonist) is used to treat diarrhea-predominant IBS in female patients. Other 5-HT\n                    <jats:sub>3<\/jats:sub>\n                    receptor antagonists are ineffective at treating IBS symptoms. The visceromotor response (VMR) to CRD in SERT-KO and wild-type (WT) rats was measured following subcutaneous (sc), intracerobroventricular (icv), or intrathecal (it) treatment with 5-HT\n                    <jats:sub>3<\/jats:sub>\n                    receptor antagonists and an agonist. Alosetron (sc) and granisetron (antagonists) caused a paradoxical increase in the VMR to CRD in SERT-KO female rats. Alosetron (sc) increased the VMR to CRD in WT male rats. Alosetron (it) increased the VMR to CRD in SERT-KO female rats only, and the 5-HT\n                    <jats:sub>3<\/jats:sub>\n                    receptor agonist SR-52772 increased the VMR to CRD in SERT-KO male rats. Depletion of spinal 5-HT using 5,7-dihydroxytryptamine prevented the increase in VMR to CRD in SERT-KO female and male rats treated it with alosetron and SR-52772, respectively. Alosetron (icv) did not affect the VMR to CRD in WT or KO female rats, but it increased the VMR in male SERT-KO but not WT male rats. These data suggest that 5-HT\n                    <jats:sub>3<\/jats:sub>\n                    receptor signaling at the dorsal spinal cord mediates visceral hypersensitivity in female SERT-KO rats. Such differences could facilitate development of sex-specific drug treatments for visceral pain.\n                  <\/jats:p>\n                  <jats:p>\n                    NEW &amp; NOTEWORTHY We studied a model of female sex-specific visceral hypersensitivity using rats that had a loss of function of the serotonin transporter (SERT) caused by gene truncation. Female SERT-KO rats exhibited visceral hypersensitivity in response to colorectal balloon distention. We found that increased 5-HT signaling at dorsal spine 5-HT\n                    <jats:sub>3<\/jats:sub>\n                    receptors was responsible for visceral hypersensitivity in female but not male SERT-KO rats.\n                  <\/jats:p>","DOI":"10.1152\/ajpgi.00131.2018","type":"journal-article","created":{"date-parts":[[2018,10,25]],"date-time":"2018-10-25T14:22:30Z","timestamp":1540477350000},"page":"G132-G143","source":"Crossref","is-referenced-by-count":24,"title":["5-HT\n                    <sub>3<\/sub>\n                    receptor signaling in serotonin transporter-knockout rats: a female sex-specific animal model of visceral hypersensitivity"],"prefix":"10.1152","volume":"316","author":[{"given":"Nadine","family":"El-Ayache","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Galligan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan"},{"name":"Neuroscience Program, Michigan State University, East Lansing, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2011.03.011"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2015.1048223"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.11-07-01881.1991"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb13263.x"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2008.08.003"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1053\/eujp.2000.0167"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.35990"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2006.10.028"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2015.00413"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2016-313425"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.2147\/CLEP.S40245"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2005.40365.x"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.5812\/aapm.42747"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i47.17693"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.0954"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2003.12.044"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-008-0244-8"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2982.1999.00148.x"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2012.05208.x"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1021\/cb300246j"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12133"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2013-305989"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.34245"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(90)90721-M"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1159\/000201377"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.114.216028"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.1996.tb00267.x"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2013.12.025"},{"key":"B29","first-page":"4581","volume":"8","author":"Gu QY","year":"2015","journal-title":"Int J Clin Exp Med"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2010.11.057"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2015.07.048"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2008.06.001"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn195"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(03)02952-4"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2004.02031.x"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2016.03.064"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1136\/gut.46.4.474"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(96)00857-6"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R112.406496"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-017-0289-8"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2012.14"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.2002.01287.x"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19981221)402:3<385::AID-CNE7>3.0.CO;2-Q"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(03)00400-1"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2016-311835"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/0168-0102(96)01034-6"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2008.05.002"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199010000-00005"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/0166-4328(96)00072-1"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2011.03.012"},{"key":"B51","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/S0022-3565(25)31262-0","volume":"205","author":"Stewart JJ","year":"1978","journal-title":"J Pharmacol Exp Ther"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2016.10.025"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-02-00708.2003"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1080\/030097400446625"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1211\/002235702320266208"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.cacc.2006.05.003"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-03-01010.2002"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2018.08.059"}],"container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpgi.00131.2018","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T21:46:59Z","timestamp":1775252819000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpgi.00131.2018"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,1]]},"references-count":58,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,1,1]]}},"alternative-id":["10.1152\/ajpgi.00131.2018"],"URL":"https:\/\/doi.org\/10.1152\/ajpgi.00131.2018","relation":{},"ISSN":["0193-1857","1522-1547"],"issn-type":[{"value":"0193-1857","type":"print"},{"value":"1522-1547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,1]]}}}