EQUILIBRATIVE ADENOSINE TRANSPORT IN RAT HEPATOCYTES AFTER CHRONIC ETHANOL FEEDING

Acute treatment of cells with ethanol in vitro inhibits adenosine upta ke via equilibrative nucleoside transporters. After longer periods of exposure to ethanol in culture, rechallenge with ethanol no longer inh ibits adenosine uptake. Herein, we have investigated the longterm effe cts of ethanol consumption in vivo on equilibrative nucleoside transpo rt. Rats were fed a liquid diet containing 35% of calories as ethanol (ethanol-fed). Control rats were pair-fed a liquid diet that isocalori cally substituted maltose dextrins for ethanol. After 4 weeks of ethan ol consumption, nucleoside transport was measured in isolated hepatocy tes. Uptake of [H-3]adenosine was lower in ethanol-fed rats compared w ith control. Influx of the nonmetabolizable nucleoside analog, [H-3]fo rmycin B, was also decreased after ethanol feeding. However, neither t he number of nitrobenzylthioinosine (NBMPR) binding sites or inhibitio n of adenosine uptake by NBMPR were affected by ethanol feeding. In co ntrols, acute treatment of isolated hepatocytes with 100 mM ethanol in hibited [H-3]adenosine uptake by 30-40%. However, in ethanol-fed rats, acute challenge with ethanol did not inhibit [H-3]adenosine uptake. T hese data demonstrate that long-term ethanol feeding decreases equilib rative nucleoside transport in hepatocytes independent of a change in the number of nucleoside transporters and renders adenosine uptake ins ensitive to inhibition by ethanol.