[Characteristic features of proton pump inhibitors in the inhibition of gastric acid secretion: long-acting and complete inhibition].
Proton pump inhibitor is a compound recently applied for the treatment of peptic ulcers for its strong action to inhibit the gastric acid secretion. It works through inhibition of H+, K(+)-ATPase, so called proton pump, on the luminal surface of secretory canaliculi in the parietal cells, showing remarkable characteristics in the inhibition of gastric acid secretion; e.g., the long-acting and complete inhibition. At neutral pH, the unionized form of this compound as a weak base is lipophilic, and passes through the cell membrane to accumulate as the ionized form in an acidic environment in the secretory canaliculi of parietal cells, where it is transformed to an active molecule which binds covalently to the active site of H+, K(+)-ATPase, forming a highly stable complex. The long-acting and complete inhibition of gastric acid secretion by this compound is derived from this physico-chemical nature. The above characteristics of the proton pump inhibitor have been confirmed with the basal, stimulated and nocturnal gastric acid secretion and the 24-hour intragastric pH of healthy volunteers by several investigators prior to its nation-wide clinical trial in Japan. On the other hand, the increased endocrine and exocrine secretion, such as pepsin secretion and gastrin release, and the increased turnover of gastrointestinal endocrine cells by this compound have been reported in animal models, probably due to its accumulation in the acidic environment.(ABSTRACT TRUNCATED AT 250 WORDS)
Ohe
K
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Health Care Center, University of Occupational and Environmental Health.
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000897:Anti-Ulcer Agents; D003692:Delayed-Action Preparations; D003864:Depression, Chemical; D005744:Gastric Acid / Q000378:metabolism*; D017506:H(+)-K(+)-Exchanging ATPase; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007329:Insulin Antagonists; D009853:Omeprazole / Q000494:pharmacology*; D010295:Parietal Cells, Gastric / Q000201:enzymology / Q000378:metabolism; D013758:Tetragastrin / Q000037:antagonists & inhibitors
D000897:Anti-Ulcer Agents; D003692:Delayed-Action Preparations; D007329:Insulin Antagonists; D013758:Tetragastrin; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase; D009853:Omeprazole