Synaptosomal uptake of choline and of gamma-aminobutyric acid: effects of ethanol and of dimethylsulfoxide.
We have characterized the interactive effects of ethanol and dimethylsulfoxide on synaptosomal uptakes of gamma-aminobutyric acid (GABA) and choline. Ethanol is a membrane-disordering agent which has been shown to inhibit synaptosomal high-affinity choline uptake at pharmacologically relevant ethanol concentrations, and to inhibit synaptosomal GABA uptake at higher ethanol concentrations. Dimethylsulfoxide (DMSO) is an organic solvent which has been shown to have a stabilizing effect on artificial phospholipid bilayers, and to have effects on conformation of and cation binding to brain (Na+, K+)-ATPase which are opposite those of ethanol. DMSO alone (2-10% v/v) inhibited synaptosomal uptakes of GABA and of choline in a concentration-dependent fashion, with choline uptake inhibited to a greater degree than GABA uptake. This result is qualitatively similar to the effects of ethanol on these uptake processes. DMSO at low concentrations (0.3-1.5% v/v) had no effect on inhibition of GABA and choline uptake by 0.6 M ethanol, and higher DMSO concentrations resulted only in further inhibition. Similarly, ethanol (0.3 M) had no effect on inhibition of GABA and choline uptake by 5% (v/v) DMSO, and higher ethanol concentrations (0.6-1.2 M) resulted only in further inhibition. We conclude that the inhibiting effects of ethanol on synaptosomal GABA and choline uptake are not reversed by DMSO.
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Department of Pathology, University of Arkansas for Medical Sciences, Little Rock.
Mrak
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D000818:Animals; D002794:Choline / Q000378:metabolism*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D066298:In Vitro Techniques; D008560:Membrane Fluidity / Q000187:drug effects; D008854:Microscopy, Electron; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D002794:Choline; D004121:Dimethyl Sulfoxide