Effects of TU-199, a novel H+,K+-ATPase inhibitor, on gastric acid secretion and gastroduodenal ulcers in rats

We studied the effects of TU-199, a novel H+, K+-ATPase inhibitor, on gastr ic acid secretion and gastroduodenal lesions in rats in comparison with tho se of omeprazole. TU-199 inhibited hog gastric H+, K+-ATPase activity and i ts potency was almost equal to that of omeprazole (IC50 = 6.2 and 4.2 mu M, respectively). In vivo, TU-199 inhibited basal gastric acid secretion in p ylorus-ligated rats in a dose-dependent manner (ED50 = 4.2 mg/kg p.o.). In gastric fistula rats, TU-199 prevented the formation of water-immersion res traint stress-, pylorus ligation-, and indomethacin-induced gastric lesions , and mepirizole-induced duodenal ulcer in rats. These antisecretory and an tiulcer effects of TU-199 were 2-4 times more potent than those of omeprazo le. The results demonstrate that TU-199 potently inhibits the acid secretio n and formation of ulcers in various experimental rat models via an inhibit ion of H+, K+-ATPase. These findings suggest that TU-199 may have a benefic ial effect against peptic ulcer disease in humans. (C) 1999 Prous Science. All rights reserved.