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	Masahiro Ono, Hiroshi Sato, Hideaki Kazumori, Mika Yuki, Mohammad Azharul Karim Rumi, Cesar Francisco Ortega-Cava, Yasunobu Ishihara, Shunji Ishihara, Kyoichi Adachi, Yoshikazu Kinoshita
Journal	The Journal of laboratory and clinical medicine (J Lab Clin Med) Vol. 142 Issue 6 Pg. 364-71 (Dec 2003) ISSN: 0022-2143 [Print] United States
PMID	14713888 (Publication Type: Journal Article)
Chemical References	Benzophenones Gastrins Membrane Glycoproteins Membrane Transport Proteins Neuropeptides Phenylurea Compounds Proliferating Cell Nuclear Antigen RNA, Messenger Receptors, Cholecystokinin S 0509 Vesicular Biogenic Amine Transport Proteins Histidine Decarboxylase Omeprazole
Topics	Animals Benzophenones (pharmacology) Cell Division (drug effects) Enterochromaffin Cells (drug effects) Gastric Mucosa (cytology, drug effects, metabolism) Gastrins (blood) Histidine Decarboxylase (genetics) Male Membrane Glycoproteins (genetics) Membrane Transport Proteins Neuropeptides Omeprazole (pharmacology) Phenylurea Compounds (pharmacology) Proliferating Cell Nuclear Antigen (analysis) RNA, Messenger (analysis) Rats Rats, Sprague-Dawley Receptors, Cholecystokinin (antagonists & inhibitors) Vesicular Biogenic Amine Transport Proteins

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