Increased calcium/calmodulin protein kinase activity in astrocytes chronically exposed to ethanol: influences on glutamate transport.
The effects of ethanol exposures on calcium/calmodulin-dependent protein kinase activity as well as its influence on glutamate uptake were determined in astrocytes prepared from neonatal rat cerebral cortex. Acute 15-min exposure to 100 mM ethanol had no effect on Ca2+/CaM-dependent protein kinase activity. However, chronic exposure to 100 mM ethanol for 4 days elicited a significant increase in the activity of this enzyme with no parallel increase in its expression. Ca2+/CaM-independent kinase activity was less than 1% of the Ca2+/CaM-dependent kinase activity and was unaffected by any of the ethanol exposures. Exposure to 100 mM ethanol for four days also resulted in a significant increase in Na+-dependent [3H]glutamate uptake which was reversed when ethanol-exposed astrocytes were co-incubated with KN-93, a specific inhibitor of Ca2+/CaM kinase. These results suggest that the effects of ethanol on glutamate transport may be mediated in part, by the level of Ca2+/CaM kinase activity.
Smith
T L
TL
Research Service, Department of Veterans Affairs Medical Center, Tucson, AZ 85723, USA.
Navratilova
E
E
D027322:Amino Acid Transport System X-AG; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D050491:Glutamate Plasma Membrane Transport Proteins; D018698:Glutamic Acid / Q000378:metabolism*; D007700:Kinetics; D051381:Rats; D012964:Sodium / Q000378:metabolism; D027981:Symporters; D013997:Time Factors
D027322:Amino Acid Transport System X-AG; D002352:Carrier Proteins; D050491:Glutamate Plasma Membrane Transport Proteins; D027981:Symporters; D000431:Ethanol; D018698:Glutamic Acid; D012964:Sodium; D017871:Calcium-Calmodulin-Dependent Protein Kinases