Chronic ethanol feeding alters the structure and function of the epidermal growth factor receptor in rat stomach

We investigated the effect of chronic ethanol feeding on the EGF receptor in rat stomach. Adult male rats were fed either an isocaloric control or ethanol (EtOH)-containing liquid diet (36% total calories as EtOH) for 4 weeks EtOH significantly reduced the specific binding of 125I-EGF to the gastric mucosal membrane (control vs. EtOH, 2.07 +/- 0.2 vs. 0.94 +/- 0.16 fmol/mg protein; p < 0.01). Scatchard analysis suggested that the lower binding might be due to the reduction of EGF receptor number, and/or the affinity of the high-affinity binding site. Western blot analysis, using anti-EGF receptor antibody, revealed four immunoreactive protein bands (180, 150, 60, and 50 kDa) in the lectin-purified gastric membrane prepared from both groups. However, the intensities of these protein bands in the EtOH-fed animals were 90% lower compared to the controls. In the EGF-responsive protein kinase assay, 32P-ATP was incubated with lectin-purified samples in the absence or presence of 1 microM EGF. EGF stimulated autophosphorylation of the EGF receptor (180 kDa) in stomach from the control groups, but not the EtOH-fed animals. This EtOH-related alteration of the gastric EGF receptor may be one of the mechanisms underlying the gastric pathology associated with alcohol abuse.