Bile reflux due to disturbed gastric movement is a cause of spontaneous gastric ulcer in W/Wv mice.
c-Kit is a receptor tyrosine kinase, and it is encoded by the mouse W locus. Mutant W/Wv mice develop spontaneous gastric antral ulcers. The aim of the present study was to investigate the pathogenesis of these gastric ulcers and to examine the effects of two antiulcer drugs; a proton pump inhibitor (2{[4-(3-methoxypropoxy)-3-methylpyridine-2-yl]methyl-sulfinyl}-1H -benzimidazole sodium salt, rabeprazole) and a mucosal protective drug (geranylgeranylacetone, GGA), on the gastric ulcers. The inhibition of the gastric acid secretion by rabeprazole (30 mg/kg body weight, subcutaneous injection once a day for six weeks) significantly increased the gastric ulcer formation compared to the controls. In contrast, the GGA treatment (100 mg/kg body weight, oral administration for six weeks) significantly inhibited the ulcer formation. Bile reflux was seen in these mutant mice, and they showed no cyclic intense contractions in the gastric antrum. These results suggest that bile reflux due to the disturbance of gastric antral movement is a cause of the spontaneous gastric ulcers in W/Wv mice.
Azuma
T
T
Second Department of Internal Medicine, Faculty of Medicine, Fukui Medical University, Japan.
Dojyo
M
M
Ito
S
S
Yamazaki
Y
Y
Miyaji
H
H
Ito
Y
Y
Suto
H
H
Kuriyama
M
M
Kato
T
T
Kohli
Y
Y
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000284:Administration, Oral; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage; D001562:Benzimidazoles / Q000008:administration & dosage; D001647:Bile Acids and Salts / Q000032:analysis; D001655:Bile Reflux / Q000150:complications* / Q000209:etiology; D004224:Diterpenes / Q000008:administration & dosage; D004353:Drug Evaluation, Preclinical; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D005769:Gastrointestinal Motility / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains / Q000502:physiology*; D009853:Omeprazole / Q000031:analogs & derivatives; D054328:Proton Pump Inhibitors; D064750:Rabeprazole; D013270:Stomach / Q000473:pathology; D013276:Stomach Ulcer / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D001647:Bile Acids and Salts; D004224:Diterpenes; D054328:Proton Pump Inhibitors; D064750:Rabeprazole; D009853:Omeprazole; C031049:geranylgeranylacetone