Effects of ethanol in vitro on rat intestinal brush-border membranes.
Ethanol, at concentrations found in the intestinal lumen after moderate drinking, has been shown to inhibit carrier-mediated intestinal transport processes. This inhibition could occur by direct interaction with membrane transporters, dissipation of the energy producing Na+ electrochemical gradient and/or nonspecific alteration of membrane integrity. The latter alteration may be reflected by changes in membrane fluidity, chemical composition or vesicular size. These possibilities were examined with studies in purified brush border membrane vesicles of rat intestine. Ethanol inhibited concentrative Na+-dependent D-glucose uptake in a dose-dependent manner. In contrast, ethanol did not inhibit concentrative D-glucose uptake under conditions of D-glucose trans-stimulation in the absence of a Na+ electrochemical gradient. Ethanol also inhibited initial, concentrative Na+-dependent taurocholic acid uptake, as well as equilibrium uptake. That ethanol exerted a dual effect on transport by increasing membrane conductance for Na+ while decreasing intravesicular space was supported by direct studies of Na+ uptake. Morphometric analysis confirmed that ethanol-treated membranes had a decreased intravesicular size when compared to untreated membranes. Finally, membrane fluidity measured by EPR showed that ethanol had a significant fluidizing effect without producing qualitative changes in membrane proteins, as determined by SDS gel electrophoresis. These results suggest that ethanol inhibits carrier-mediated transport by dissipation of the Na+ electrochemical gradient and alteration of membrane integrity rather than by direct interaction with membrane transporter.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D000431:Ethanol / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000302:isolation & purification; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008970:Molecular Weight; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism; D013656:Taurocholic Acid / Q000378:metabolism
D008565:Membrane Proteins; D000431:Ethanol; D013656:Taurocholic Acid; D012964:Sodium; D005947:Glucose