title: Mechanism of gastric antisecretory effect of SCH 28080.
abstract: The mechanism of the gastric antisecretory action of SCH 28080 has been studied utilizing two different in vitro test systems, isolated and enriched parietal cells from the guinea-pig and guinea-pig gastric membranes purified and enriched with K+/H+-ATPase. In guinea-pig isolated and enriched parietal cells SCH 28080 inhibited the acid response to histamine and high K+ concentrations with IC50 values not significantly different from each other. SCH 28080 inhibited the purified K+/H+-ATPase measured in the presence of 5 mM KCl with an IC50 value of 1.3 microM. Kinetic studies indicated a competitive inhibition of ATPase by SCH 28080 with respect to K+. Studies on Na+/K+-ATPase showed that this enzyme was only slightly depressed by SCH 28080. It is concluded that SCH 28080 acts with high selectivity on the parietal cell K%/H+-ATPase, establishing its antisecretory effect by a competitive interaction with the high affinity K+-site of the gastric ATPase.
mesh_terms: D009597:4-Nitrophenylphosphatase / Q000037:antagonists & inhibitors; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000302:isolation & purification; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D004285:Dogs; D005750:Gastric Juice / Q000378:metabolism*; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism
chemical_list: D000897:Anti-Ulcer Agents; D007093:Imidazoles; D011506:Proteins; C035235:Sch 28080; D009597:4-Nitrophenylphosphatase; D000251:Adenosine Triphosphatases; C029321:calcium potassium ATPase