[Effect of a new antiulcer drug, leminoprazole, on the gastric mucosal H+,K(+)-ATPase activity in rats].
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 microM and 24 microM, 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.
Matsukura
H
H
Research Laboratories, Nippon Chemiphar Co., Ltd., Saitama, Japan.
Masuda
M
M
Uchida
A
A
Kamishiro
T
T
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; C089751:leminoprazole; D017506:H(+)-K(+)-Exchanging ATPase