{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T18:19:09Z","timestamp":1790273949479,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":3011,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2000,11]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item>\n<jats:p>5\u2010HT<jats:sub>4<\/jats:sub> receptors mediate circular muscle relaxation in both human and canine large intestine, but this phenomenon alone can not explain the improvement in colonic motility induced by selective 5\u2010HT<jats:sub>4<\/jats:sub> receptor agonists <jats:italic>in vivo<\/jats:italic>. We set out to characterize 5\u2010HT<jats:sub>4<\/jats:sub> receptor\u2010mediated effects in longitudinal muscle strips of canine and human large intestine.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>Electrical field stimulation (EFS) was applied providing submaximal isotonic contractions. <jats:sc>L<\/jats:sc>\u2010NOARG (0.1\u2003m<jats:sc>M<\/jats:sc>) was continuously present in the organ bath to preclude nitric oxide\u2010induced relaxation to EFS.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>The selective 5\u2010HT<jats:sub>4<\/jats:sub> receptor agonist prucalopride (0.3\u2003\u03bc<jats:sc>M<\/jats:sc>) enhanced EFS\u2010evoked contractions, that were antagonized in both preparations by the selective 5\u2010HT<jats:sub>4<\/jats:sub> receptor antagonist GR\u2003113808 (0.1\u2003\u03bc<jats:sc>M<\/jats:sc>). The prucalopride\u2010induced increase was present in canine ascending and descending colon, but absent in rectum. Regional differences in response to prucalopride were not observed in human ascending and sigmoid colon and rectum. Incubation with atropine (1\u2003\u03bc<jats:sc>M<\/jats:sc>) or tetrodotoxin (0.3\u2003\u03bc<jats:sc>M<\/jats:sc>) inhibited EFS\u2010induced contractions, which were then unaffected by prucalopride (0.3\u2003\u03bc<jats:sc>M<\/jats:sc>) in both tissues.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>In the presence of methysergide (3\u2003\u03bc<jats:sc>M<\/jats:sc>; both tissues) and granisetron (0.3\u2003\u03bc<jats:sc>M<\/jats:sc>; only human tissues), 5\u2010HT (0.3\u2003\u03bc<jats:sc>M<\/jats:sc>) enhanced EFS\u2010induced contractions, an effect that was antagonized by GR\u2003113808 (0.1\u2003\u03bc<jats:sc>M<\/jats:sc>). In the presence of atropine or tetrodotoxin, EFS\u2010induced contractions were inhibited, leaving 5\u2010HT (0.3\u2003\u03bc<jats:sc>M<\/jats:sc>) ineffective in both preparations.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>This study demonstrates for the first time that in human and canine large intestine, 5\u2010HT<jats:sub>4<\/jats:sub> receptors are located on cholinergic neurones, presumably mediating facilitating release of acetylcholine, resulting in enhanced longitudinal muscle contractility. This study and previous circular muscle strip studies suggest that 5\u2010HT<jats:sub>4<\/jats:sub> receptor agonism facilitates colonic propulsion <jats:italic>via<\/jats:italic> a coordinated combination of inhibition of circumferential resistance and enhancement of longitudinal muscle contractility.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2000) <jats:bold>131<\/jats:bold>, 927\u2013932; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0703615\">10.1038\/sj.bjp.0703615<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0703615","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T20:58:48Z","timestamp":1106945928000},"page":"927-932","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":83,"title":["5\u2010HT<sub>4<\/sub> receptors on cholinergic nerves involved in contractility of canine and human large intestine longitudinal muscle"],"prefix":"10.1111","volume":"131","author":[{"given":"N H","family":"Prins","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L M A","family":"Akkermans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R A","family":"Lefebvre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J A J","family":"Schuurkes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00169544"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2000.740478.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1995.tb05782.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1998.70062252.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(96)00466-9"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(96)00297-X"},{"key":"e_1_2_7_8_1","first-page":"A705","article-title":"Serotonin 5\u2010HT4 receptors mediate the R093877\u2010induced changes in contractile patterns in the canine colon","volume":"112","author":"BRIEJER M.R.","year":"1998","journal-title":"Gastroenterology"},{"key":"e_1_2_7_9_1","first-page":"A704","article-title":"In vitro pharmacology of the novel enterokinetic R093877","volume":"112","author":"BRIEJER M.R.","year":"1998","journal-title":"Gastroenterology"},{"key":"e_1_2_7_10_1","first-page":"A705","article-title":"Dose\u2010dependent effects after oral and intravenous administration of R093877 on colonic motility in conscious dogs","volume":"112","author":"BRIEJER M.R.","year":"1998","journal-title":"Gastroenterology"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(94)90031-0"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(96)00474-8"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1985.tb05100.x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1996.tb15631.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-3623(94)90130-9"},{"key":"e_1_2_7_16_1","first-page":"880","article-title":"A nonclassical 5\u2010hydroxytryptamine receptor positively coupled with adenylate cyclase in the central nervous system","volume":"34","author":"DUMUIS A.","year":"1988","journal-title":"Mol. 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