{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T17:03:34Z","timestamp":1773421414423,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,6,21]],"date-time":"2012-06-21T00:00:00Z","timestamp":1340236800000},"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":[[2012,7]]},"abstract":"<jats:sec><jats:title>BACKGROUND AND PURPOSE<\/jats:title><jats:p>JNJ\u201026070109 [(R)4\u2010bromo\u2010N\u2010[1\u2010(2,4\u2010difluoro\u2010phenyl)\u2010ethyl]\u20102\u2010(quinoxaline\u20105\u2010sulfonylamino)\u2010benzamide] is a novel antagonist at cholecystokinin CCK<jats:sub>2<\/jats:sub> receptors with good pharmacokinetic properties and represents a novel mechanism for the treatment of gastro\u2010oesophageal reflux disease (GORD). The purpose of the present study was to determine whether chronic treatment with JNJ\u201026070109 could prevent, as well as treat, acid rebound in rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>EXPERIMENTAL APPROACH<\/jats:title><jats:p>A chronic fistula was surgically inserted into the stomach of rats to enable the measurement of acid secretion under basal, pentagastrin and histamine\u2010stimulated conditions. JNJ\u201026070109 and omeprazole were administered separately and in combination.<\/jats:p><\/jats:sec><jats:sec><jats:title>KEY RESULTS<\/jats:title><jats:p>Sustained administration of omeprazole alone and in combination with JNJ\u201026070109 inhibited gastric acid secretion by &gt;90%. However, 3 days after withdrawing treatment, there was a rebound hypersecretion by \u223c1.5\u2010fold in omeprazole\u2010treated animals. No such acid rebound was observed with JNJ\u201026070109 alone or with co\u2010administration of JNJ\u201026070109 and omeprazole. The anti\u2010trophic effects of JNJ\u201026070109 in the gastric mucosal paralleled the effects on acid rebound. Administration of JNJ\u201026070109 for 3 days after cessation of omeprazole prevented the occurrence of acid rebound. Interestingly, chronic, but not acute, treatment with JNJ\u201026070109 also inhibited histamine\u2010stimulated acid secretion.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS AND IMPLICATIONS<\/jats:title><jats:p>Chronic administration of JNJ\u201026070109 effectively inhibited gastric acid secretion and suppressed proton pump inhibitor (PPI)\u2010induced acid rebound in the rat. This work advances the field by demonstrating that modest doses of a competitive CCK<jats:sub>2<\/jats:sub> receptor antagonist have significant and functionally important anti\u2010trophic actions in the gastric mucosa. These properties make JNJ\u201026070109 a suitable candidate for clinical investigation for the treatment of GORD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1476-5381.2012.01878.x","type":"journal-article","created":{"date-parts":[[2012,2,2]],"date-time":"2012-02-02T15:57:59Z","timestamp":1328198279000},"page":"1684-1693","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The cholecystokinin CCK<sub>2<\/sub> receptor antagonist, JNJ\u201026070109, inhibits gastric acid secretion and prevents omeprazole\u2010induced acid rebound in the rat"],"prefix":"10.1111","volume":"166","author":[{"given":"TD","family":"Barrett","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G","family":"Lagaud","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"Wagaman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JM","family":"Freedman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L","family":"Andries","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MC","family":"Rizzolio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MF","family":"Morton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"NP","family":"Shankley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,6,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01649_1.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2006.03084.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(87)90044-7"},{"key":"e_1_2_8_5_1","first-page":"383","article-title":"Effect on gastric pH of repeated doses of YF476, a new gastrin antagonist, compared with omeprazole and placebo","volume":"49","author":"Boyce M","year":"2000","journal-title":"Br J Clin Pharmacol"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00489.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2003.11.012"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.63.1.119"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02093608"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0773.2001.d01-161.x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(99)70118-6"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12576-008-0001-y"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703342"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1159\/000199615"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(88)80066-0"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.regpep.2005.02.013"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706196"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2011.02.003"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.110.178483"},{"key":"e_1_2_8_20_1","first-page":"G699","article-title":"Gastrin receptor antagonist YM022 prevents hypersecretion after long\u2010term acid suppression","volume":"269","author":"Nishida A","year":"1995","journal-title":"Am J Physiol"},{"key":"e_1_2_8_21_1","first-page":"745","article-title":"International Union of Pharmacology. 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