Inhibitory Effect of Rebamipide on Helicobacter pylori Induced Release of Leukotriene D4

ABSTRACT

It has been implicated that leukotrienes play roles in the pathogenesis of gastritis and gastric ulceration associated with Helicobacter pylori (H. pylori). Rebamipide is being used as an antiulcer drug but it's mechanism of action has not been understood well. One possible mechanism of action of this drug is to inhibit the cellular release of leukotrienes by various stimuli, particularly H. pylori. In the present study, attempts were made to test this possibility and the results are as follows. When Kato III cells (gastric adenoma cells) were stimulated by H. pylori, leukotriene D4 (LTD4) was released and rebamipide inhibited this release dose-dependently. Similar experiment was performed on neutrophils because the infilteration of neutrophils is a common phenomenon in H. pylori-infected gasrtric tissues. Neutrophils released LTD4 when these cells were stimulated by H. pylori and rebamipide also inhibited this release. Furthermore, rebamipide inhibited the release of LTD from neutrophils induced by calcium ionophore A23187 and arachidonic acid. The results suggest that rebamipide has the action to inhibit the release of LTD4 from various cells and this action may contribute in part to prevent the ulcerogenesis induced by H. pylori.