Helicobacter pylori Urease Inhibition by Rabeprazole, a Proton Pump Inhibitor.

Abstract

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 (I50s) were found to be 0.29, 5.4, 9.3 and 0.3 microM 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 beta-mercaptoethanol, glutathione and dithiothreitol. Moreover, the addition of beta-mercaptoethanol recovered the urease activity inhibited by rabeprazole. From these results, we expected that rabeprazole inhibited H. pylori urease activity by forming disulfide bonds between it and the active site of the enzyme.

Helicobacter pyloriDetection and Antimicrobial Susceptibility Testing

“…By changing the milieu where the bacteria are present, especially the antrum, PPI renders it inhospitable and the bacterial load decreases. In addition, PPI themselves may have antiurease properties (533). Another reason for a false-negative test is the presence of intestinal metaplasia, which also corresponds to an inhospitable environment for H. pylori.…”

A Novel Action of the Proton Pump Inhibitor Rabeprazole and Its Thioether Derivative against the Motility of Helicobacter pylori

“…PPIs used were omeprazole (OPZ), lansoprazole (LPZ), and RPZ (6,26). RPZ-TH (6,26), which is secreted into gastric juice, was also used.…”

“…PPIs used were omeprazole (OPZ), lansoprazole (LPZ), and RPZ (6,26). RPZ-TH (6,26), which is secreted into gastric juice, was also used. H 2 blockers and anti-H. pylori agents used, respectively, included cimetidine, ranitidine, and famotidine and clarithromycin (CAM), amoxicillin (AMPC), and metronidazole (MNZ).…”

“…Prolonged incubation with RPZ or RPZ-TH inhibited bacterial growth of only H. pylori, except for a turbid colony mutant. The results indicate that RPZ and RPZ-TH have a characteristic inhibitory effect against the motility of H. pylori (spiral-shaped bacteria), which is distinguished from that against bacterial growth.Helicobacter pylori, which colonizes the gastric mucosa, is closely associated with gastritis and peptic ulcers (7,17) and is even a bacterial risk factor for gastric cancer (9,10,24,25,27 (1,6,11,14,15,23) as well as urease activity (16,19,26) …”

“…PPIs inhibit the H ϩ , K ϩ ATPase of parietal cells. In addition to this, PPIs inhibit H. pylori cell growth (1,6,11,14,15,23) as well as urease activity (16,19,26) …”