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 exam ined in comparison with those of omeprazole. YJA20379-4 markedly inhib ited the H+/K+-ATPase activity in a concentration-dependent manner and the inhibitory effect was increased under a weak acidic condition; th e IC50 values were 32 and 81 mu M 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 inhibitor y concentration (MIC, 3.9-11.7 mu g/ml) was at least 3 times more pote nt than that of omeprazole. In pylorus ligated rats, YJA20379-4 inhibi ted basal gastric acid secretion when administered by the intraduodena l route (ED50: 23.6 mg/kg), In experimental ulcer models, YJA20379-3 a dministered by the oral route dose-dependently prevented the developme nt of gastro-duodenal lesions in rats, Moreover, repeated administrati on of YJA20379-4 promoted the healing of gastric ulcers induced by ace tic acid. On the basis of the data obtained, it is suggested that YJA2 0379-4 has a wide spectrum of antiulcer activities, and its mode of an tiulcer actions is dependent on the inhibition of H+/K+-ATPase activit y and H. pylori growth and the enhancement of a mucosal defense, Thus, YJA20379-4 might prove to be a beneficial therapy for gastritis and p eptic ulcer diseases.