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To make progress, the actions of existing drugs and new therapeutic candidates need to be understood in human isolated stomach.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Neuromuscular activities were evoked in human gastric antrum circular muscle by electrical field stimulation (<jats:styled-content style=\"fixed-case\">EFS<\/jats:styled-content>), defined phenotypically using pharmacological tools.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">EFS<\/jats:styled-content>evoked cholinergically mediated contractions, attenuated by simultaneous nitrergic activation. The 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content><jats:sub>4<\/jats:sub>receptor agonist\/D<jats:sub>2<\/jats:sub>antagonist metoclopramide and the selective 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content><jats:sub>4<\/jats:sub>agonist prucalopride, facilitated contractions in the absence (respectively, E<jats:sub>max<\/jats:sub>95\u00a0\u00b1\u00a029% and 42\u00a0\u00b1\u00a09%,<jats:italic>n<\/jats:italic>\u00a0=\u00a03\u20136 each concentration) and presence (139\u00a0\u00b1\u00a038%, 55\u00a0\u00b1\u00a013%,<jats:italic>n<\/jats:italic>\u00a0=\u00a03\u20135) of the<jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content>synthase inhibitor L\u2010<jats:styled-content style=\"fixed-case\">NAME<\/jats:styled-content>, without affecting submaximal contractions to carbachol; the 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content><jats:sub>4<\/jats:sub>antagonist<jats:styled-content style=\"fixed-case\">SB<\/jats:styled-content>204070 prevented facilitation by metoclopramide 100\u00a0<jats:italic>\u03bc<\/jats:italic>M (respectively, \u22125 (range \u221226 to 34) and 167 (12\u20131327)% in presence and absence;<jats:italic>n<\/jats:italic>\u00a0=\u00a05\u20136). The selective motilin receptor agonist camicinal provided considerably greater facilitation (478 (12\u20132080)% at 30\u00a0<jats:italic>\u03bc<\/jats:italic>M,<jats:italic>n<\/jats:italic>\u00a0=\u00a08). Domperidone (0.001\u2013100\u00a0<jats:italic>\u03bc<\/jats:italic>M;<jats:italic>n<\/jats:italic>\u00a0=\u00a03\u20136) and acylated or des\u2010acylated ghrelin (1\u2013300\u00a0nM;<jats:italic>n<\/jats:italic>\u00a0=\u00a02\u20134) had no consistent activity, even with protease inhibitors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content><jats:sub>4<\/jats:sub>receptor agonists show different efficacies. Motilin receptor activation has greater potential to increase gastric emptying, whereas ghrelin and D<jats:sub>2<\/jats:sub>receptor antagonism have no direct activity. Drugs stimulating human gastric motility directly can act regardless of disease mechanisms, whereas drugs without direct activity but an ability to block nausea\/vomiting may be effective only if these symptoms exist.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.12338","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T04:11:01Z","timestamp":1398053461000},"page":"851-861","source":"Crossref","is-referenced-by-count":27,"title":["Drugs acting at 5\u2010<scp>HT<\/scp><sub>4<\/sub>, D<sub>2<\/sub>, motilin, and ghrelin receptors differ markedly in how they affect neuromuscular functions in human isolated stomach"],"prefix":"10.1111","volume":"26","author":[{"given":"J.","family":"Broad","sequence":"first","affiliation":[{"name":"Neurogastroenterology Group Blizard Institute Barts &amp; The London School of Medicine and Dentistry Queen Mary University of London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"G\u00f3ralczyk","sequence":"additional","affiliation":[{"name":"Bariatric Surgery Department Homerton University Hospital London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Mannur","sequence":"additional","affiliation":[{"name":"Bariatric Surgery Department Homerton University Hospital London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. E.","family":"Dukes","sequence":"additional","affiliation":[{"name":"Academic DPU GlaxoSmithKline Research Triangle Park NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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