Inhibition of H+,K+-ATPase by methyl(E)-2-(3,4-dimethoxystyryl)-benzimidazole-4-carboxylate (ALE-36).
ALE-36, as well as omeprazole and SCH 28080, markedly inhibited the [14C]aminopyrine (AP) accumulation induced by dibutyryl cyclic AMP (dbcAMP) and H+,K+-ATPase activity in a concentration-dependent manner. The inhibitory effect of omeprazole on the dbcAMP-induced [14C]AP accumulation was reversed by treatment with beta-mercaptoethanol, but those of ALE-36 and SCH 28080 were not. ALE-36 and SCH 28080 did not inhibit dog renal Na+,K+-ATPase activity, while omeprazole and ouabain did inhibit this enzyme activity. These results suggest that the inhibitory action of ALE-36 on acid secretion is due to the specific inhibition of gastric H+,K+-ATPase, the manner being different from in the case of omeprazole.
Yamamoto
O
O
Research Laboratories, Nippon Shinyaku Co., Ltd., Kyoto, Japan.
Tanaka
H
H
Ueda
F
F
Kimura
K
K
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D017506:H(+)-K(+)-Exchanging ATPase; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology; D008297:Male; D009853:Omeprazole / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010295:Parietal Cells, Gastric / Q000201:enzymology / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D007093:Imidazoles; C035235:Sch 28080; D000632:Aminopyrine; C061955:methyl 2-(3,4-dimethoxystyryl)benzimidazole-4-carboxylate; D010042:Ouabain; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase; D000254:Sodium-Potassium-Exchanging ATPase; D009853:Omeprazole