PT - JOURNAL ARTICLE AU - Chi Dae Kim AU - Ki Whan Hong TI - Preventive Effect of Rebamipide on Gastric Mucosal Cell Damage Evoked by Activation of Formyl-Methionyl-Leucyl-Phenylalanine Receptors of Rabbit Neutrophils DP - 1997 Apr 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 478--483 VI - 281 IP - 1 4099 - http://jpet.aspetjournals.org/content/281/1/478.short 4100 - http://jpet.aspetjournals.org/content/281/1/478.full SO - J Pharmacol Exp Ther1997 Apr 01; 281 AB - We investigated the underlying mechanism by which rebamipide exerts a preventive effect on neutrophil-mediated gastric mucosal cell damage. The release of 2′,7′-bis-(2-carboxyethyl)-5-(and -6)-carboxyfluorescein (an index of cytotoxicity) was significantly increased by 16.7% (P < .05) when 2′,7′-bis-(2-carboxyethyl)-5-(and -6)-carboxyfluorescein-acetomethyl ester (5 μM) loaded gastric mucosal cells were incubated with neutrophils (5 × 106 cells/well) that were activated by cytochalasin B (5 μM) and formyl-methionyl-leucyl-phenylalanine (fMLP) (1 nM). In thein vitro study, upon application of cytochalasin B and fMLP, formation of superoxide anion and release of myeloperoxidase increased with increased neutrophil aggregation. These parameters were attenuated by pretreatment with rebamipide (100–1000 μM) in a concentration-dependent manner. In the Scatchard analysis, the maximum binding of [3H]fMLP to neutrophils decreased from 0.57 to 0.44 pmol/2 × 106 cells (P < .05) by application of rebamipide (300 μM) with little change inKD. Neutrophils isolated from rabbits orally treated with rebamipide (100 mg/kg for 3 days) also showed a decrease in the production of superoxide anion upon stimulation with fMLP and a decrease in the binding of [3H]fMLP to its receptors on the neutrophil plasma membrane (0.59–0.45 pmol/2 × 106 cells, P < .05). Taken together, it is suggested that the inhibitory effect of rebamipide on the neutrophil-mediated gastric mucosal cell injury is due, in part, to alterations in the neutrophil membrane that ultimately result in a decrease in the number of binding sites for fMLP to its receptors. The American Society for Pharmacology and Experimental Therapeutics