Ethanol modulates N-methyl-D-aspartate-evoked arachidonic acid release from neurones.
Glutamate-evokes a Ca2+-dependent release of arachidonic acid from cultured neurones via the activation of NMDA and AMPA receptors. In this study we investigated whether exposing cultured striatal neurones either acutely or chronically to ethanol would modify these responses. Acute ethanol (100 mM, 15 min) inhibited the liberation of arachidonic acid evoked by a maximally effective concentration of glutamate, an affect which appeared to be mediated primarily by a reduction in NMDA receptor responsiveness. In contrast, chronic ethanol exposure caused a dose-dependent increase in the glutamate, N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) evoked release of arachidonic acid, although ethanol was less potent at the AMPA response. Basal responses were not altered by acute or chronic ethanol and the concentrations of ethanol employed were not toxic. Chronic ethanol (100 mM, 48 h) increased NMDA-mediated neuronal damage at sub-maximal concentrations of the agonist, suggesting that an enhanced mobilisation of arachidonic acid may underly the potentiated excitotoxic neuronal loss observed following exposure to ethanol.
Navamani
M
M
Division of Biochemistry and Molecular Biology, UMDS, Guy's Medical School, London, UK.
Morgan
M
M
Williams
R J
RJ
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000633:toxicity*; D003342:Corpus Striatum / Q000187:drug effects* / Q000196:embryology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000633:toxicity*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D002492:Central Nervous System Depressants; D018690:Excitatory Amino Acid Agonists; D016718:Arachidonic Acid; D000431:Ethanol; D018698:Glutamic Acid; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid