Effects of chronic ethanol consumption on the partition of lipophilic compounds into erythrocyte membranes

Abstract

We have previously reported that chronic ethanol intoxication decreases the binding of various lipophilic substances to membranes of synaptosome and hepatic mitochondria. To determine whether this is a widespread effect, we used the quenching of the steady state fluorescence of membrane-bound diphenylhexatriene by halothane and the partitioning spin probe, 5-doxyl decane, to estimate the concentration of these compounds in erythrocyte plasma membranes. Membranes from ethanol-fed rats were resistant to the quenching of fluorescence by halothane or halothane plus 5-doxyl decane, compared with those from control animals, indicating lower quencher concentrations in the membranes of treated rats. These findings were confirmed by direct measurement of the partition of radiolabeled halothane into the membranes and by direct determination of the partition parameter of 5-doxyl decane by electron paramagnetic resonance spectroscopy. Halothane decreased the fluorescence lifetime to a larger extent in control membranes than in those from ethanol-fed rats. When various effects of halothane were expressed as a function of the concentration of halothane in the membrane, rather than the external buffer, no differences between membranes from control and treated rats were found. These data demonstrate that chronic ethanol intoxication decreases the partition of certain lipophilic compounds into the plasma membranes of erythrocytes, but that, at equivalent concentrations within the membrane, the interactions of halothane and the dye are comparable in both types of membranes. We suggest that the decreased partition of lipophilic compounds into biologic membranes is a widespread adaptive response to chronic ethanol intoxication and may play an important role in the resistance of such membranes to disordering after chronic ethanol ingestion.