title: Effect of a gastrin/cholecystokinin B receptor antagonist, S-0509, on the omeprazole-induced proliferation of gastric mucosa in rats.
abstract: Hypergastrinemia is known to cause hyperplasia of the gastric mucosa, especially in gastric enterochromaffinlike (ECL) cells. In some clinical conditions causing hypergastrinemia, such as long-term gastric-acid inhibition and gastric-mucosa atrophy, hyperplastic ECL cells may develop into gastric carcinoid tumors. A newly developed gastrin-receptor antagonist, S-0509, has been reported to block gastrin-induced stimulation of gastric-acid secretion. We therefore investigated whether S-0509 inhibits the omeprazole- and gastrin-stimulated hyperproliferation of gastric mucosa, especially of ECL cells. Daily administration of omeprazole and gastrin in male Sprague-Dawley rats induced marked hypergastrinemia and increased proliferation of gastric-mucosa cells. The numbers of ECL cells and of ECL cells producing messenger RNA for regenerating gene, a potent growth factor for gastric-mucosa cells, were also augmented by long-term administration of omeprazole and gastrin. Coadministration of S-0509 with omeprazole or gastrin almost completely inhibited the omeprazole- and gastrin-induced changes in gastric mucosa, including mucosal thickening and ECL hyperplasia. S-0509 did not induce gastric-mucosa atrophy, even when administered for as long as 4 weeks. In summary, we have found that a newly developed gastrin receptor antagonist, S-0509, inhibits omeprazole- and gastrin-induced mucosal hyperplasia, especially ECL-cell hyperplasia, in rats.
authors.affiliation: The Department of Medicine II, Shimane Medical University School of Medicine, Izumo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ono
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sato
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kazumori
authors.forename: Mika
authors.initials: M
authors.lastname: Yuki
authors.forename: Mohammad Azharul Karim
authors.initials: MA
authors.lastname: Rumi
authors.forename: Cesar Francisco
authors.initials: CF
authors.lastname: Ortega-Cava
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Ishihara
authors.forename: Shunji
authors.initials: S
authors.lastname: Ishihara
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Adachi
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kinoshita
mesh_terms: D000818:Animals; D001577:Benzophenones / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004759:Enterochromaffin Cells / Q000187:drug effects; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005755:Gastrins / Q000097:blood; D006640:Histidine Decarboxylase / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D009853:Omeprazole / Q000494:pharmacology*; D010671:Phenylurea Compounds / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D050492:Vesicular Biogenic Amine Transport Proteins
chemical_list: D001577:Benzophenones; D005755:Gastrins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D010671:Phenylurea Compounds; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D011949:Receptors, Cholecystokinin; C109118:S 0509; D050492:Vesicular Biogenic Amine Transport Proteins; D006640:Histidine Decarboxylase; D009853:Omeprazole