Effects of the seafood toxin domoic acid on glutamate uptake by rat astrocytes.
Pronounced glutamic acid uptake was observed after only 15 min with glutamate concentrations of 60 nmol/mg protein when astrocytes were incubated with 1 mM glutamic acid. The uptake increased with time to a steady-state glutamate level of above 160 nmol/mg protein by 45 min. The uptake was energy dependent. Reduced temperature (0 degrees C) and ouabain (100 microM) inhibited uptake by 86.7% (P<0.001; n=18) and 84.4% (P<0.001; n=18), respectively, when compared with controls. After exposure of astrocytes to glutamate (1 mM) in the incubation medium, in the presence of domoic acid (10 and 100 microM) at 5 and 60 min, domoic acid (10 microM) elevated glutamate uptake by 64.0% (P<0.05; n=34) at 5 min but decreased glutamate uptake by 47.8% (P<0.01; n=19) at 60 min compared with controls. A higher dose of domoic acid (100 microM) decreased glutamate uptake by 49.6% (P<0.01; n=20) and 61.3% (P<0.001; n=20) at 5 and 60 min, respectively, compared with controls. This study suggests that domoic acid may induce neurotoxicity because of the failure of astrocytes to remove extracellular glutamate. This may contribute to excitotoxic injury.
Ross
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Division of Toxicological Research, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Washington, DC 20204, USA.
Johnson
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Sapienza
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Kim
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D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D002478:Cells, Cultured; D003080:Cold Temperature; D004336:Drug Antagonism; D018698:Glutamic Acid / Q000378:metabolism*; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000633:toxicity*; D008387:Marine Toxins / Q000633:toxicity*; D009498:Neurotoxins / Q000633:toxicity*; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D013997:Time Factors
D008387:Marine Toxins; D009498:Neurotoxins; D018698:Glutamic Acid; D010042:Ouabain; C012301:domoic acid; D007608:Kainic Acid