Helicobacter pylori Urease Inhibition by Rabeprazole, a Proton Pump Inhibitor

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We investigated the inhibitory effects of four gastric proton pump inhibitors (PPIs) : rabeprazole, a novel benzimidazole PPI, omeprazole, lansoprazole and AG-2000,on the urease activity of Helicobacter pylori (H. pylori). Their 50% inhibitory concentrations (I_<50>s) were found to be 0.29,5.4,9.3 and 0.3 μM respectively. Rabeprazole and omeprazole were also potent inhibitors of Jack bean and Proteus mirabilis cellular ureases. The thioether derivative of rabeprazole, one of its metabolites, had no inhibitory effect on H.pylori urease, despite being reported as a more potent inhibitor of H. pylori growth than rabeprazole. The inhibitory effect of rabeprazole was prevented completely and reversed considerably by the addition of sulfhydryl compounds, such as β-mercaptoethanol, glutathione and dithiothreitol. Moreover, the addition of β-mercaptoethanol recovered the urease activity inhibited by rabeprazole. From these results, we expected that rabeprazole inhibited H. pyloriurease activity by forming disulfide bonds between it and the active site of the enzyme.
1995-08-15