Mechanism of gastric antisecretory effects of nolinium bromide

Nolinium bromide [2-(3,4-dichlorophenyl amino)-quinolizium bromide] inhibits histamine-stimulated gastric acid secretion by bullfrog gastric mucosa in vitro. Nolinium bromide was effective from both the secretory and the nutrient sides of the chambered mucosa. The inhibitory effects of secretory but not the nutrient nolinium bromide could be largely reversed by elevating the concentration of K+ of the secretory solution. The mechanisms of the inhibitory effects of nutrient nolinium bromide appeared to be different than those from the secretory side. Gastric microsomes highly enriched in H+, K+-ATPase activity (which has been identified as the proton pump) were used to elucidate the mechanism of nolinium bromide action. Nolinium bromide inhibits in a dose-dependent manner both the gastric H+, K+-ATPase activity and H+ uptake ability of the microsomes. Increasing concentrations of K+ could reverse the nolinium bromide inhibition of both the H+, K+-ATPase activity and vesicular H+ transport. The data strongly suggest that nolinium bromide interferes primarily with the K+-dependent phosphatase step and thereby reduces the turnover of the enzyme. The data have been discussed in the light of our present day knowledge on gastric H+ transport.