Ethanol alters glutamate but not adenosine uptake in rat astrocytes: evidence for protein kinase C involvement.
Glutamate is the primary excitatory neurotransmitter in brain. By stimulating neuronal activity, glutamate increases cellular energy utilization, enhances ATP hydrolysis and promotes the formation of adenosine. Adenosine has receptor-mediated effects that reduce or oppose the excitatory effects of glutamate. As a possible mechanism for ethanol's ability to inhibit excitatory effects of glutamate and enhance inhibitory effects of adenosine, we tested the hypothesis that ethanol promotes [3H]glutamate uptake and inhibits [3H]adenosine uptake. Using primary cultures of rat astrocytes, we found that acute treatment with ethanol (50 mM, 30 min) inhibited [3H]glutamate uptake and reduced protein kinase C (PKC)-induced stimulation of [3H]glutamate uptake. Prolonged treatment (50 mM, 3 day) with ethanol, however, increased both [3H]glutamate uptake and PKC activity. Contrary to other cell types, neither acute or chronic ethanol exposure affected [3H]adenosine uptake in astrocytes. These data indicate that in rat cortical astrocytes ethanol affects [3H]glutamate uptake but not [3H]adenosine uptake by affecting PKC modulation of transporter activity.
Othman
Timothy
T
Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada.
Sinclair
Christopher J D
CJ
Haughey
Norman
N
Geiger
Jonathan D
JD
Parkinson
Fiona E
FE
D000241:Adenosine / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000470:Alkaloids; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D053119:Benzophenanthridines; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D004622:Embryo, Mammalian; D000431:Ethanol / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D007700:Kinetics; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D053119:Benzophenanthridines; D010617:Phenanthridines; D000431:Ethanol; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; C016299:chelerythrine; D011493:Protein Kinase C; D000241:Adenosine; D013755:Tetradecanoylphorbol Acetate