title: Preventive effect of rebamipide on gastric mucosal cell damage evoked by activation of formyl-methionyl-leucyl-phenylalanine receptors of rabbit neutrophils.
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 microM) loaded gastric mucosal cells were incubated with neutrophils (5 x 10(6) cells/well) that were activated by cytochalasin B (5 microM) and formyl-methionyl-leucyl-phenylalanine (fMLP) (1 nM). In the in 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 microM) 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 x 10(6) cells (P < .05) by application of rebamipide (300 microM) with little change in K(D). 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 x 10(6) 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.
authors.affiliation: Department of Pharmacology, College of Medicine, Pusan National University, Korea.
authors.forename: C D
authors.initials: CD
authors.lastname: Kim
authors.forename: K W
authors.initials: KW
authors.lastname: Hong
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000633:toxicity; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D015363:Quinolones / Q000633:toxicity*; D011817:Rabbits; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000187:drug effects*; D018000:Receptors, Peptide / Q000187:drug effects*; D012969:Sodium Fluoride / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000897:Anti-Ulcer Agents; D015363:Quinolones; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D012969:Sodium Fluoride; C052785:rebamipide; D013755:Tetradecanoylphorbol Acetate; D000409:Alanine