TIME-DEPENDENT ALTERATION OF EPIDERMAL GROWTH-FACTOR RECEPTOR IN RAT STOMACH BY ETHANOL FEEDING

This study investigated the time-dependent effects of ethanol (EtOH) f eeding on epidermal growth factor binding and epidermal growth factor- mediated functions in the stomach. Adult male rats were fed either an isocaloric control or EtOH-containing liquid diet (36% total calories as EtOH) for 2, 4 and 6 weeks. At the end of each feeding period, anim als were sacrificed and the stomach was dissected for the sample prepa ration. EtOH caused a time-dependent alteration (r = 0.89) of the I-12 5-epidermal growth factor binding to the gastric mucosal membrane (% c ontrol: week 2, 114%; week 4, 64% and week 6, 45%*, n = 5, *P < 0.05) . Protein kinase analysis also showed that EtOH caused a time-dependen t decrease of epidermal growth factor-stimulated autophosphorylation o f epidermal growth factor receptor protein (180 kDa) during three feed ing periods. Western blot analysis, using anti-tyrosine phosphorylated epidermal growth factor receptor (active form) antibody, revealed a m ajor immunoreactive protein band (180 kDa) in all samples pre-incubate d with 1 mu M epidermal growth factor. Consistent with data from kinas e analysis, treatment of EtOH decreased the immunoreactivity of the ac tive form of epidermal growth factor receptor (180 kDa) in the stomach . In conclusion, EtOH feeding caused a time-dependent alteration of ep idermal growth factor receptor in the stomach, which may be one of the mechanisms underlying the gastric pathology associated with alcohol a buse. (C) 1997 Elsevier Science Ireland Ltd.