@article {Kim478, author = {Chi Dae Kim and Ki Whan Hong}, title = {Preventive Effect of Rebamipide on Gastric Mucosal Cell Damage Evoked by Activation of Formyl-Methionyl-Leucyl-Phenylalanine Receptors of Rabbit Neutrophils}, volume = {281}, number = {1}, pages = {478--483}, year = {1997}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {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 {\texttimes} 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{\textendash}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 {\texttimes} 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{\textendash}0.45 pmol/2 {\texttimes} 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}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/281/1/478}, eprint = {https://jpet.aspetjournals.org/content/281/1/478.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }