Helicobacter pylori augments the acid inhibitory effect of omeprazole on parietal cells and gastric H(+)/K(+)-ATPase.
BACKGROUND
In duodenal ulcer patients, intragastric acidity during omeprazole treatment is significantly lower before Helicobacter pylori eradication than after cure.


OBJECTIVE
To determine if H pylori enhances the acid inhibitory potency of omeprazole in isolated parietal cells and on H(+)/K(+)-ATPase.


METHODS
Rat parietal cells and pig gastric membrane vesicles enriched in H(+)/K(+)-ATPase activity were incubated with H pylori and the H pylori fatty acid cis 9,10-methyleneoctadecanoic acid (MOA), and the inhibitory effects of omeprazole on parietal cell acid production, H(+)/K(+)-ATPase enzyme activity, and ATPase mediated proton transport were assessed.


RESULTS
In isolated parietal cells, H pylori and MOA increased the acid inhibitory potency of omeprazole 1.8 fold. H pylori did not affect the inhibitory potency of omeprazole on H(+)/K(+)-ATPase enzyme activity. In proton transport studies, H pylori (intact bacteria and sonicate) and MOA accelerated the onset of the inhibitory effect of omeprazole and enhanced the proton dissipation rate in response to omeprazole. H. pylori itself increased proton permeability at the vesicle membrane.


CONCLUSIONS
Our results show that H pylori augments the acid inhibitory potency of omeprazole in parietal cells and enhances omeprazole induced proton efflux rate from gastric membrane vesicles. We suggest that omeprazole unmasks the permanent effect of H pylori on proton permeability at the apical parietal cell membrane, which is counteracted in the absence of a proton pump inhibitor by a reserve H(+)/K(+)-ATPase capacity.
Beil
W
W
Department of General Pharmacology, Hannover Medical School, Hannover, Germany. Beil.Winfried@MHHannover.de
Sewing
K F
KF
Busche
R
R
Wagner
S
S
D000818:Animals; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D017506:H(+)-K(+)-Exchanging ATPase / Q000187:drug effects* / Q000502:physiology; D016480:Helicobacter pylori / Q000502:physiology*; D008297:Male; D009853:Omeprazole / Q000494:pharmacology*; D010295:Parietal Cells, Gastric / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013229:Stearic Acids / Q000494:pharmacology; D013552:Swine
D004791:Enzyme Inhibitors; D013229:Stearic Acids; D017506:H(+)-K(+)-Exchanging ATPase; D009853:Omeprazole