Ethanol effects on synaptic glutamate receptor function and on membrane lipid organization.
The enhancement of L-glutamic acid binding activity of brain synaptic membranes by low concentrations of ethanol (less than 50 mM) and the decrease in binding at high concentrations (greater than 100 mM) was not due to a direct action by ethanol on the glutamate binding protein. Biphasic effects of ethanol on membrane protein complexes such as the glutamate binding sites might be the result of biphasic changes in membrane lipid organization. Low ethanol concentrations (0.1-4.0 mM) were shown to decrease fatty acid chain motion detected by the EPR probe 5-doxyl stearic acid, whereas high concentrations (greater than 400 mM) increased lipid motion in egg phosphatidylcholine liposomes. The function of the L-glutamate receptor-ion channel complex in the presence of ethanol was also determined by measuring the changes in thiocyanate (SCN-) influx brought about by L-glutamate or ethanol. A low concentration of ethanol (9.4 mM) diminished the L-glutamate-induced depolarization of synaptic membranes, while a high concentration (93.7 mM) increased the passive SCN-influx and produced a transient overshoot in glutamate-stimulated SCN-flux.
D000818:Animals; D001921:Brain / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D000431:Ethanol / Q000633:toxicity*; D005227:Fatty Acids / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D007473:Ion Channels / Q000187:drug effects; D008081:Liposomes / Q000378:metabolism; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects; D010713:Phosphatidylcholines / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects*; D017470:Receptors, Glutamate; D013569:Synapses / Q000187:drug effects*; D013572:Synaptic Vesicles / Q000187:drug effects
D005227:Fatty Acids; D005971:Glutamates; D007473:Ion Channels; D008081:Liposomes; D008563:Membrane Lipids; D008565:Membrane Proteins; D010713:Phosphatidylcholines; D011956:Receptors, Cell Surface; D017470:Receptors, Glutamate; D000431:Ethanol; D018698:Glutamic Acid