Ethanol reduces kainate-evoked glutamate secretion in rat hippocampal astrocytes

Abstract

In this study we have used rat hippocampal astrocytes in culture to investigate the effect of ethanol on kainate-induced glutamate secretion. Our results show that kainate (10 μM to 500 μM) stimulated glutamate release from astrocytes. Preincubation of astrocytes in the presence of ethanol induced a concentration-dependent (1mM-50mM) inhibition of glutamate release caused by stimulation of cells with 100 μM kainate. Inhibition of alcohol-dehydrogenase, by preincubation of astrocytes in the presence of 4-methylpyrazole (1mM), abolished ethanol-induced inhibition of glutamate release in response to kainate. On the other hand, preincubation of astrocytes in the presence of the antioxidant cinnamtannin B-1 (10 μM) also blocked ethanol inhibitory action on glutamate release in response to kainate. Ethanol (50mM) reduced Ca(2+) mobilization in response to kainate, whereas cinnamtannin B-1 reversed the inhibitory action of ethanol on Ca(2+) mobilization by kainate. Our results are consistent with an inhibitory action of ethanol on glutamate secretion from hippocampal astrocytes. The inhibitory effects of ethanol are probably due to its oxidative metabolization, involves reactive oxygen species production, and a lower Ca(2+) mobilization by kainate. Taking into account the pivotal role that astrocytes play within the central nervous system, especially in relation to neurons, the negative effects of ethanol on the release of glutamate might affect neuron-glia communication in the hippocampus, which might lead to functional defects in the brain.