Chronic exposure of cerebellar granule cells to ethanol results in increased N-methyl-D-aspartate receptor function.
Chronic exposure of cerebellar granule cells to ethanol results in increased N-methyl-D-aspartate receptor function.
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发表时间：
1992-06
影响因子：
3.6
通讯作者：
K. Iorio;Leslie Reinlib;B. Tabakoff;P. Hoffman
中科院分区：
文献类型：
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作者：
K. Iorio;Leslie Reinlib;B. Tabakoff;P. Hoffman
在原代培养的小脑颗粒细胞中，N-甲基-D-天冬氨酸(NMDA)受体的激活导致钙内流。以前的工作表明，这种反应被急性暴露在低浓度乙醇中选择性地抑制。目前的结果表明，细胞对NMDA的反应(用Fura-2荧光法测量为细胞内钙浓度的增加)在体外慢性暴露于乙醇(100 mM，2-4天；20 mM，3天或更多天)后显著增强。这种增强与NMDA受体数量的增加是一致的，受体的性质没有变化。具体地说，竞争性或非竞争性拮抗剂对NMDA和甘氨酸的EC50值没有变化，也没有改变对NMDA反应的抑制程度。在细胞长期接触乙醇后，急性乙醇抑制NMDA反应的能力也没有改变。此外，慢性乙醇暴露并不能改变细胞在30 mM KCl中暴露后细胞内钙离子的去极化依赖性增加。这些数据表明，慢性酒精暴露会选择性上调NMDA受体的功能。在完好无损的动物中，这种变化可能与乙醇戒断的特定症状有关，即戒断发作。
In primary cultures of cerebellar granule cells, activation of the N-methyl-D-aspartate (NMDA) receptor leads to Ca2+ influx. Previous work showed that this response is selectively inhibited by acute exposure to low concentrations of ethanol. The present results demonstrate that the response to NMDA (measured as an increase in intracellular Ca2+ concentration, using fura-2 fluorescence) is significantly enhanced after chronic in vitro exposure of the cells to ethanol (100 mM for 2-4 days; 20 mM for 3 or more days). This enhancement is consistent with an increased number of NMDA receptors, with no change in receptor properties. Specifically, there was no change in the EC50 values for NMDA and glycine or in the magnitude of inhibition of the NMDA response by competitive or uncompetitive antagonists. There was also no change in the ability of acute ethanol to inhibit the NMDA response after chronic exposure of the cells to ethanol. Furthermore, chronic ethanol exposure did not alter depolarization-dependent increases in intracellular Ca2+ observed after exposure of the cells to 30 mM KCl. The data suggest that chronic ethanol exposure produces a selective up-regulation of NMDA receptor function. In the intact animal, such a change may be associated with particular symptoms of ethanol withdrawal, i.e., withdrawal seizures.