[Possible mechanisms for (H+ + K+)-ATPase inhibition by proton pump inhibitors, omeprazole, lansoprazole and SCH 28080].
Proton pump inhibitors are classified into two distinct types, and the mechanisms are reviewed. Substituted benzimidazole such as omeprazole and lansorrazole, inhibit (H+ + K+)-ATPase by reacting with SH groups of enzyme after the drugs are transformed into their active forms in the acidic environment of the intracellular canaliculi of parietal cells. This type of enzyme inhibition results in potent and long-lasting inhibition of gastric acid secretion. On the other hand, substituted imidazo pyridines, such as SCH 28080, inhibit (H+ + K+)-ATPase by competing with K+. This inhibition is reversible and the antisecretory effect is short-lived. Recent studies on DNA cloning and sequencing for (H+ + K+)-ATPase have led to a better understanding of enzyme structure and also the sites of action of the proton pump inhibitors.
Nagaya
H
H
Biology Research Laboratories, Takeda Chemical Industries Ltd.
Satoh
H
H
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001711:Biotransformation; D004220:Disulfides; D005744:Gastric Acid / Q000378:metabolism*; D017506:H(+)-K(+)-Exchanging ATPase; D007093:Imidazoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D064747:Lansoprazole; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D004220:Disulfides; D007093:Imidazoles; C035235:Sch 28080; D064747:Lansoprazole; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase; D009853:Omeprazole; D011188:Potassium