title: Effects of TU-199, a novel H+, K(+)-ATPase inhibitor, on gastric acid secretion and gastroduodenal ulcers in rats.
abstract: We studied the effects of TU-199, a novel H+, K(+)-ATPase inhibitor, on gastric acid secretion and gastroduodenal lesions in rats in comparison with those of omeprazole. TU-199 inhibited hog gastric H+, K(+)-ATPase activity and its potency was almost equal to that of omeprazole (IC50 = 6.2 and 4.2 microM, respectively). In vivo, TU-199 inhibited basal gastric acid secretion in pylorus-ligated rats in a dose-dependent manner (ED50 = 4.2 mg/kg p.o.). In gastric fistula rats. TU-199 (2.5 and 5 mg/kg i.d.) also inhibited gastric acid secretion stimulated by histamine, carbachol or tetragastrin. Furthermore, TU-199 prevented the formation of water-immersion restraint stress-, pylorus ligation- and indomethacin-induced gastric lesions, and mepirizole-induced duodenal ulcer in rats. These antisecretory and antiulcer effects of TU-199 were 2-4 times more potent than those of omeprazole. The results demonstrate that TU-199 potently inhibits the acid secretion and formation of ulcers in various experimental rat models via an inhibition of H+, K(+)-ATPase. These findings suggest that TU-199 may have a beneficial effect against peptic ulcer disease in humans.
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000818:Animals; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D005744:Gastric Acid / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009853:Omeprazole / Q000627:therapeutic use*; D010437:Peptic Ulcer / Q000188:drug therapy* / Q000378:metabolism; D054328:Proton Pump Inhibitors; D011725:Pyridines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley