Effect of a new antiulcer drug, leminoprazole, on the gastric mucosal H+, K+-ATPase activity in rats.

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  • 新規抗潰よう剤レミノプラゾールのラット胃粘膜Ｈ｀＋´，Ｋ｀＋´‐ＡＴＰａｓｅ阻害作用の検討
  • シンキ コウ カイヨウザイ レミノプラゾール ノ ラット イ ネンマク H +

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The inhibitory action of leminoprazole on the activity of rat gastric mucosal H+, K+-ATPase was investigated in vitro and ex vivo. Leminoprazole and omeprazole concentration-dependently inhibited the H+, K+-ATPase activity, and their IC50 values were 31 μM and 24 μM, respectively, at pH7.4. Leminoprazole dose-dependently inhibited the H+, K+-ATPase activity at 3 and 6 hr after the administration at 10-100 mg/kg, p.o. Leminoprazole (60 mg/kg, p.o.) inhibited the H+, K+-ATPase activity persistently, and the duration of its inhibitory action was much longer than that of omeprazole (30 mg/kg, p.o.). In pylorus-ligated rats, good correlations between the respective inhibitory rates against gastric acid output and H+, K+-ATPase activity was found after the administration of leminoprazole. These results suggest that leminoprazole inhibits the gastric acid secretion by its ability to inhibit the H+, K+-ATPase activity in rats; its inhibitory activity was comparable to that of omeprazole. In addition, leminoprazole (100 mg/kg) inhibited the H+, K+-ATPase activity even when administered intragastrically after pylorus-ligation, suggesting that this drug can inhibit H+, K+-ATPase activity directly from the gastric lumen. Moreover, leminoprazole (100 mg/kg, p.o.) when administered repeatedly for 2 or 4 weeks inhibited the H+, K+-ATPase activity to the same degree as the single administration.

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