{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T03:46:35Z","timestamp":1791085595091,"version":"4.1.0"},"reference-count":76,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":1124,"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":[[2006,1]]},"abstract":"<jats:p><jats:list list-type=\"explicit-label\"><jats:list-item><jats:p>In this study, we aimed to characterize<jats:italic>in vitro<\/jats:italic>the effects of the benzofuran 5\u2010HT<jats:sub>4<\/jats:sub>receptor agonists prucalopride, R149402 and R199715 and the indolic agents tegaserod and 5\u2010HT in the atria of young pigs (10\u201311 weeks) and newborn piglets.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>In the paced left atrium of young pigs, only 5\u2010HT results in positive inotropic responses when administered cumulatively (maximal effect relative to isoprenaline=53%, pEC<jats:sub>50<\/jats:sub>=6.8); however, all agonists showed lusitropic effects. Noncumulative administration results in greater positive inotropic responses for 5\u2010HT and induces moderate positive inotropic responses for the other agonists; these responses fade.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Phosphodiesterase (PDE) enzyme inhibition with 3\u2010isobutyl\u20101\u2010methylxanthine (IBMX; 20\u2003<jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc>) enhances the responses to cumulatively administered 5\u2010HT (maximal effect=89%, pEC<jats:sub>50<\/jats:sub>=7.7) and reveals clear positive inotropic effects for prucalopride, tegaserod, R149402 and R199715; fading is abolished. The maximal effect of the benzofurans is less pronounced than that of the indoles.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>In the spontaneously beating right atrium of young pigs, all agonists show chronotropic activity when administered cumulatively in the absence of IBMX, without fade. Benzofurans behaved as partial agonists compared to 5\u2010HT (maximal effect=54%, pEC<jats:sub>50<\/jats:sub>=6.5).<\/jats:p><\/jats:list-item><jats:list-item><jats:p>In newborns, the inotropic activity of the agonists in the IBMX\u2010treated left atrium was less pronounced than in the young pig; the same applied for the chronotropic response in the right atrium, except for 5\u2010HT.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>In conclusion, the atrial responses to 5\u2010HT<jats:sub>4<\/jats:sub>receptor activation increase in the first months of life; the inotropic response is regulated by PDEs. Prucalopride, R149402 and R199715 are partial agonists compared to 5\u2010HT.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic>(2006)<jats:bold>147<\/jats:bold>, 140\u2013157. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0706497\">10.1038\/sj.bjp.0706497<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0706497","type":"journal-article","created":{"date-parts":[[2005,12,5]],"date-time":"2005-12-05T16:12:20Z","timestamp":1133799140000},"page":"140-157","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Porcine left atrial and sinoatrial 5\u2010HT<sub>4<\/sub>receptor\u2010induced responses: fading of the response and influence of development"],"prefix":"10.1111","volume":"147","author":[{"given":"Joris H","family":"De Maeyer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roel","family":"Straetemans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan A J","family":"Schuurkes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain A","family":"Lefebvre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"808","article-title":"Characterization of homologous 5\u2010hydroxytryptamine4 receptor desensitization in colliculi neurons","volume":"42","author":"ANSANAY H.","year":"1992","journal-title":"Mol. Pharmacol."},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002100000299"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2005.01.003"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705929"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2005.04.040"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1998.70062252.x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(97)00820-X"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568007043482615"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-004-0919-4"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-004-0963-0"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(01)01087-1"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20040846"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2005.04.009"},{"key":"e_1_2_8_15_1","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/S0026-895X(24)23188-6","article-title":"Novel brain\u2010specific 5\u2010HT4 receptor splice variants show marked constitutive activity: role of the C\u2010terminal intracellular domain","volume":"55","author":"CLAEYSEN S.","year":"1999","journal-title":"Mol. Pharmacol."},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.8.1921"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(00)89081-1"},{"key":"e_1_2_8_18_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0031-6997(24)01478-9","article-title":"Evolving concepts in G protein\u2010coupled receptor endocytosis: the role in receptor desensitization and signaling","volume":"53","author":"FERGUSON S.S.","year":"2001","journal-title":"Pharmacol. Rev."},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1994.tb14064.x"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2490709"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1995.tb07280.x"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s003950170081"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0160-5402(83)90004-9"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1213\/01.ANE.0000136466.85913.3C"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.65.5.1313"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00169000"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01379"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.1.295"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.99.1.65"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00169055"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(94)90058-2"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb15900.x"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00169181"},{"key":"e_1_2_8_34_1","first-page":"664","article-title":"A receptor for 5\u2010HT in human atrium","volume":"98","author":"KAUMANN A.J.","year":"1989","journal-title":"Br. J. Pharmacol."},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00170877"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-662-05553-3_6"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1990.tb14108.x"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00167212"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(00)89020-3"},{"key":"e_1_2_8_40_1","first-page":"214","article-title":"Theoretical effects of single and multiple transducer receptor coupling proteins on estimates of the relative potency of agonists","volume":"35","author":"KENAKIN T.P.","year":"1989","journal-title":"Mol. Pharmacol."},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-200311000-00013"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm020099f"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(92)90293-D"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2004.05.002"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2828(86)80946-4"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1993.tb13916.x"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(01)00095-X"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703101"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705061"},{"key":"e_1_2_8_50_1","first-page":"346","article-title":"Serotonin increases calcium current in human atrial myocytes via the newly described 5\u2010hydroxytryptamine4 receptors","volume":"41","author":"OUADID H.","year":"1992","journal-title":"Mol. Pharmacol."},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00168912"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705553"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.104.076869"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1074683"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.61.1.85"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4419-0318-1"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(98)00198-9"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.104.008748"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2004.11.017"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.100.19.2010"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7258(01)00169-3"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M405697200"},{"key":"e_1_2_8_63_1","first-page":"977","article-title":"Homologous desensitization of 5\u2010hydroxytryptamine4 receptors in rat esophagus: functional and second messenger studies","volume":"272","author":"RONDE P.","year":"1995","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00176614"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.92.9.2526"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1054-3589(08)60178-7"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/0163-7258(94)00005-N"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(93)90417-G"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00169001"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004240100617"},{"key":"e_1_2_8_71_1","volume-title":"Linear Mixed Models in Practice. A SAS\u2010Oriented Approach","author":"VERBEKE G.","year":"2005"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(01)00154-X"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1991.tb12140.x"},{"key":"e_1_2_8_74_1","volume-title":"Linear and Nonlinear Models for the Analysis of Repeated Measurements","author":"VONESH E.F.","year":"1997"},{"key":"e_1_2_8_75_1","first-page":"436","article-title":"Serotonin, If and human atrial arrhythmia","volume":"40","author":"WORKMAN A.J.","year":"1998","journal-title":"Cardiovasc. Res."},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1831718100"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1069982"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0706497","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0706497","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/sj.bjp.0706497","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T05:13:40Z","timestamp":1736140420000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1038\/sj.bjp.0706497"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,1]]},"references-count":76,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2006,1]]}},"alternative-id":["10.1038\/sj.bjp.0706497"],"URL":"https:\/\/doi.org\/10.1038\/sj.bjp.0706497","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,1]]},"assertion":[{"value":"2009-01-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}