Inhibition of N-methyl-D-aspartate- and kainate-evoked noradrenaline release in human cerebral cortex slices by ethanol.
The effect of ethanol on the release of noradrenaline evoked by various stimuli was investigated in human cerebral cortical slices from patients undergoing neurosurgery. The slices were preincubated with [3H]noradrenaline and then superfused. Tritium overflow was stimulated by exposure to N-methyl-D-aspartate (NMDA; in slices superfused without Mg2+), kainic acid, veratridine or by increasing the K+ concentration. The NMDA-evoked tritium overflow was concentration-dependently inhibited by ethanol; an inhibition by 37% occurred at 48 mmol/l ethanol. This ethanol concentration was not yet effective when kainic acid was used for stimulation, but ethanol 150 mmol/l strongly inhibited the tritium overflow evoked by kainic acid as well. The tritium overflow evoked by veratridine or high K+ was not affected by ethanol in the concentration range investigated. These findings are compatible with the suggestion that the NMDA receptor and, with less susceptibility, the kainate receptor are sites of action underlying the effect of ethanol in the human brain.
Fink
K
K
Institute of Pharmacology and Toxicology, University of Bonn, Federal Republic of Germany.
Schultheiss
R
R
Göthert
M
M
D000328:Adult; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000378:metabolism; D014701:Veratridine / Q000494:pharmacology
D000431:Ethanol; D007608:Kainic Acid; D016202:N-Methylaspartate; D009638:Norepinephrine; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D014701:Veratridine