Effect of a gastrin/cholecystokinin B receptor antagonist, S-0509, on the omeprazole-induced proliferation of gastric mucosa in rats.
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.
Ono
Masahiro
M
The Department of Medicine II, Shimane Medical University School of Medicine, Izumo, Japan.
Sato
Hiroshi
H
Kazumori
Hideaki
H
Yuki
Mika
M
Rumi
Mohammad Azharul Karim
MA
Ortega-Cava
Cesar Francisco
CF
Ishihara
Yasunobu
Y
Ishihara
Shunji
S
Adachi
Kyoichi
K
Kinoshita
Yoshikazu
Y
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
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