Effects of YJA20379-4 on gastric secretion, Helicobacter pylori growth and various gastric and duodenal lesions in rats.
Effects of a newly synthesized antiulcer agent, YJA20379-4, on gastric proton pump (H+/K+-ATPase) activity, Helicobacter pylori (H. pylori) growth, gastric acid secretion, and gastro-duodenal lesions, were examined in comparison with those of omeprazole. YJA20379-4 markedly inhibited the H+/K+-ATPase activity in a concentration-dependent manner and the inhibitory effect was increased under a weak acidic condition; the IC50 values were 32 and 81 microM at pH 6.4 and 7.4, respectively. The inhibition was completely antagonized by 0.5 mM dithiothreitol (DTT). In addition, YJA20379-4 showed a significant anti-H. pylori activity determined by the agar dilution method. The value of minimum inhibitory concentration (MIC, 3.9-11.7 microg/ml) was at least 3 times more potent than that of omeprazole. In pylorus ligated rats, YJA20379-4 inhibited basal gastric acid secretion when administered by the intraduodenal route (ED50: 23.6 mg/kg). In experimental ulcer models, YJA20379-4 administered by the oral route dose-dependently prevented the development of gastro-duodenal lesions in rats. Moreover, repeated administration of YJA20379-4 promoted the healing of gastric ulcers induced by acetic acid. On the basis of the data obtained, it is suggested that YJA20379-4 has a wide spectrum of antiulcer activities, and its mode of antiulcer actions is dependent on the inhibition of H+/K+-ATPase activity and H. pylori growth and the enhancement of a mucosal defense. Thus, YJA20379-4 might prove to be a beneficial therapy for gastritis and peptic ulcer diseases.
Woo
T W
TW
Pharmacology and Toxicology Laboratory, Research and Development Center, Yung-Jin Pharmaceutical Co., Ltd., Kyunggi-Do, Korea.
Chang
M S
MS
Chung
Y K
YK
Kim
K B
KB
Sohn
S K
SK
Kim
S G
SG
Choi
W S
WS
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D004229:Dithiothreitol / Q000494:pharmacology; D004381:Duodenal Ulcer / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016480:Helicobacter pylori / Q000187:drug effects / Q000254:growth & development*; D007101:Immersion; D008297:Male; D008826:Microbial Sensitivity Tests; D009853:Omeprazole / Q000494:pharmacology; D054328:Proton Pump Inhibitors; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000209:etiology / Q000517:prevention & control*; D013315:Stress, Psychological / Q000150:complications; D013439:Sulfhydryl Reagents / Q000494:pharmacology
D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D054328:Proton Pump Inhibitors; D013439:Sulfhydryl Reagents; C113784:YJA 20379-4; D009853:Omeprazole; D004229:Dithiothreitol