Mechanism of gastric antisecretory effect of SCH 28080.
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.
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
D000897:Anti-Ulcer Agents; D007093:Imidazoles; D011506:Proteins; C035235:Sch 28080; D009597:4-Nitrophenylphosphatase; D000251:Adenosine Triphosphatases; C029321:calcium potassium ATPase