ZONAL DIFFERENCES IN ETHANOL-INDUCED IMPAIRMENTS IN FLUID-PHASE ENDOCYTOSIS IN RAT HEPATOCYTES

We have previously shown that ethanol administration impairs the proce sses of fluid-phase endocytosis (FPE) and receptor-mediated endocytosi s (RME) in isolated rat hepatocytes after as early as 1 week of ethano l administration. The defects in RME were most prominent in the perive nule (PV) region of the liver lobule, the area wherein alcoholic liver disease has been shown to start and predominate. We undertook the pre sent study to see if changes in FPE were likewise more apparent in the PV versus the periportal (PP) region of the liver. For these studies, we fed male Sprague-Dawley rats with an ethanol-supplemented liquid d iet or an isocaloric control diet for 1 or 5 weeks. PV and PP hepatocy tes were isolated using a digitonin-collagenase perfusion method. Inte rnalization and efflux of the marker dye, Lucifer Yellow, was then exa mined in the cell populations. After as early as 1 week of feeding, ce lls from the PV region in ethanol-fed animals showed dramatic impairme nts in the net internalization of dye, compared with PV cells from the pair-fed controls, and these changes persisted throughout the 5-week feeding period. In contrast, internalization of Lucifer Yellow in cell s from the PP region of the liver were not different between control a nd ethanol animals. Because net internalization represents the balance between uptake into the cells versus efflux from the cells, we examin ed these components individually. Early uptake of the dye into the cel l was not altered by ethanol treatment. The decreased net internalizat ion seemed to be caused by enhanced efflux of the dye, which was signi ficantly increased in PV cells, compared with the same cell type in co ntrol animals. Cells from the PP region of the ethanol-fed animals did not exhibit altered efflux after either 1 or 5 weeks of feeding. Thes e results indicate that ethanol-induced impairments in FPE are more dr amatic in the PV region of the liver, and these impairments seem to re sult from an ethanol-induced enhancement of efflux.