{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:09:50Z","timestamp":1792271390487,"version":"4.4.0"},"reference-count":35,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2013,3,25]],"date-time":"2013-03-25T00:00:00Z","timestamp":1364169600000},"content-version":"vor","delay-in-days":0,"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":[[2013,4]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>The antibiotic azithromycin is a suggested alternative to erythromycin for treating patients with delayed gastric emptying. However, although hypothesized to activate motilin receptors, supportive evidence is unavailable. This was investigated using recombinant and naturally expressed motilin receptors in human stomach, comparing azithromycin with erythromycin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>[<jats:sup>125<\/jats:sup><jats:styled-content style=\"fixed-case\">I<\/jats:styled-content>]\u2010motilin binding and calcium flux experiments were conducted using human recombinant motilin receptors in <jats:styled-content style=\"fixed-case\">CHO<\/jats:styled-content> cells. Neuromuscular activities were studied using circular muscle of human gastric antrum, after electrical field stimulation (<jats:styled-content style=\"fixed-case\">EFS<\/jats:styled-content>) of intrinsic nerves.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Azithromycin (1\u2013100\u2009\u03bc<jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>) and erythromycin (3\u201330\u2009\u03bc<jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>) concentration\u2010dependently displaced [<jats:sup>125<\/jats:sup><jats:styled-content style=\"fixed-case\">I<\/jats:styled-content>]\u2010motilin binding to the motilin receptor (52 \u00b1 7 and 58 \u00b1 18% displacement at 100 and 30\u2009\u03bc<jats:styled-content style=\"fixed-case\">M<\/jats:styled-content> respectively). Azithromycin, erythromycin and motilin concentration\u2010dependently caused short\u2010lived increases in intracellular [<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>a<jats:sup>2+<\/jats:sup>] in cells expressing the motilin receptor. E<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content><jats:sub>50<\/jats:sub> values were, respectively, 2.9, 0.92 and 0.036\u2009\u03bc<jats:styled-content style=\"fixed-case\">M<\/jats:styled-content> (<jats:italic>n<\/jats:italic> = 3 each); and maximal activities were similar. In human stomach, <jats:styled-content style=\"fixed-case\">EFS<\/jats:styled-content> evoked cholinergically mediated contractions, attenuated by simultaneous nitrergic activation. Azithromycin and erythromycin lactobionate (30\u2013300\u2009\u03bc<jats:styled-content style=\"fixed-case\">M<\/jats:styled-content> each) facilitated these contractions (apparent <jats:italic><jats:styled-content style=\"fixed-case\">E<\/jats:styled-content><\/jats:italic><jats:sub>max<\/jats:sub> values of 2007 \u00b1 396 and 1924 \u00b1 1375%, <jats:italic>n<\/jats:italic> = 3\u20134 each concentration, respectively). These actions were slow in onset and faded slowly. The higher concentrations also evoked short\u2010lived muscle contraction. Contractions to a submaximally effective concentration of carbachol were unaffected by either drug.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Azithromcyin activates human recombinant motilin receptors in therapeutically relevant concentrations, similar to erythromycin. In humans, gastric antrum azithromycin caused long\u2010lasting facilitation of cholinergic activity. These actions explain the gastric prokinetic activity of azithromycin.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12077","type":"journal-article","created":{"date-parts":[[2012,11,29]],"date-time":"2012-11-29T02:10:51Z","timestamp":1354155051000},"page":"1859-1867","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":88,"title":["The antibiotic azithromycin is a motilin receptor agonist in human stomach: comparison with erythromycin"],"prefix":"10.1111","volume":"168","author":[{"given":"John","family":"Broad","sequence":"first","affiliation":[{"name":"Neurogastroenterology Group Blizard Institute Barts and The London School of Medicine and Dentistry Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth J","family":"Sanger","sequence":"additional","affiliation":[{"name":"Neurogastroenterology Group Blizard Institute Barts and The London School of Medicine and Dentistry Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,3,25]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2005.078121"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2004.01.008"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01649_1.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2012.02009.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161212803216915"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3109\/00365521.2012.654402"},{"key":"e_1_2_8_8_1","first-page":"130","article-title":"Prokinetic effect of clarithromycin and azithromycin \u2013 in vitro study on rabbit duodenum","volume":"22","author":"Chiragh S","year":"2006","journal-title":"Biomedica"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.43.3.395"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705505"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5423.2184"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1681.1999.03002.x"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkl537"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(91)90401-I"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707118"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.5056\/jnm.2010.16.4.407"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-009-0725-4"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.2000.278.1.G18"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-009-1038-3"},{"key":"e_1_2_8_20_1","volume-title":"Macrolide Antibiotics: Chemistry, Biology and Practice","author":"Omura S","year":"2002"},{"key":"e_1_2_8_21_1","first-page":"G470","article-title":"Erythromycin is a motilin receptor agonist","volume":"257","author":"Peeters T","year":"1989","journal-title":"Am J Physiol"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa040582"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1003833"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2011-300926"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2007.10.024"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2008.01084.x"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2009.01270.x"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12075"},{"key":"e_1_2_8_29_1","first-page":"121","article-title":"Comparison of the effects of midecamycin acetate and azithromycin on gastrointestinal motility in man","volume":"20","author":"Sifrim D","year":"1994","journal-title":"Drugs Exp Clin Res"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.104.081497"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(97)01317-4"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01576.x"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6468(09)04802-4"},{"key":"e_1_2_8_34_1","first-page":"356","article-title":"Distribution of orally administered azithromycin in various blood compartments","volume":"32","author":"Wildfeuer A","year":"1994","journal-title":"Int J Clin Pharmacol Ther"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.2000.278.4.L726"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389200043335450"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbph.12077","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.12077","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T04:29:07Z","timestamp":1698640147000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.12077"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,3,25]]},"references-count":35,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2013,4]]}},"alternative-id":["10.1111\/bph.12077"],"URL":"https:\/\/doi.org\/10.1111\/bph.12077","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,3,25]]},"assertion":[{"value":"2012-06-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-11-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-03-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}