Regulation of glutamate uptake in astrocytes continuously exposed to ethanol.
CNS glutamatergic transmission is altered by chronic ethanol intake and may underlie the behavioral hyperactivity associated with ethanol withdrawal. Because astrocytes regulate extracellular glutamate levels, the aim of this investigation was to characterize the effects of in vitro ethanol exposure on Na+-dependent glutamate uptake parameters in astrocytes. Ethanol exposure elicited a time and concentration-dependent increase in the maximal uptake capacity, Vmax, for [3H] glutamate, which was reversed upon withdrawal of ethanol from the media. None of the ethanol exposures had any effect on the Km for this process. In addition, the ethanol-induced increase in Vmax for glutamate was reversed by the protein kinase C inhibitors, calphostin C and bisindolylmaleimide, and was not associated with an increase in the expression of either of the major glutamate transporter proteins, GLT-1 or GLAST.
Smith
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Department of Veterans Affairs Medical Center and The Department of Pharmacology, University of Arizona, Tucson 85724, USA.
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D004789:Enzyme Activation; D000431:Ethanol / Q000494:pharmacology*; D005110:Extracellular Space / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000378:metabolism
D000431:Ethanol; D018698:Glutamic Acid; D012964:Sodium; D011493:Protein Kinase C