Effects of prenatal ethanol exposure on N-methyl-D-aspartate-mediated calcium entry into dissociated neurons.
Effects of prenatal ethanol exposure on N-methyl-D-aspartate-mediated calcium entry into dissociated neurons.
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发表时间：
1994-12
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通讯作者：
Y. H. Lee;K. Spuhler-Phillips;P. Randall;S. W. Leslie
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作者：
Y. H. Lee;K. Spuhler-Phillips;P. Randall;S. W. Leslie
研究了产前乙醇暴露对N-甲基-D-天冬氨酸（NMDA）激活的游离神经元钙内流的影响。从出生前乙醇暴露、成对喂养对照组和随意对照组的小于1日龄幼仔中分离的脑细胞，并加载fura-2。产前乙醇暴露显着降低了NMDA受体介导的钙离子内流相比，两对喂养和随意对照组。为了确定产前乙醇暴露对NMDA介导的离子通道减少的机制，研究了NMDA受体的可能调节位点。甘氨酸（0.1，1，10和100 μ M）增加钙进入乙醇和对照组在同等程度上，但没有扭转产前乙醇暴露的影响。此外，低浓度的MK 801 [（+）-5-甲基-10，11-二氢-5H-二苯并[a，d]-环庚烯-5-10-亚胺马来酸氢盐]（25和50 nM）未进一步抑制钙内流，但显著抑制对照组反应。Mg++显示出类似的结果。随着Mg++浓度的增加，三组中的钙内流趋于收敛。因此，这些结果表明，产前乙醇暴露抑制NMDA受体介导的离子通道的功能，可能通过改变离子通道本身的结构特性和/或通过与内离子通道的Mg++或MK 801激活的调节位点，而不是甘氨酸位点相互作用。
The effects of prenatal ethanol exposure on N-methyl-D-aspartate (NMDA)-activated calcium entry into dissociated neurons were studied. Dissociated brain cells were isolated from less than 1-day-old pups from prenatally ethanol-exposed, pair-fed control and ad libitum control groups and loaded with fura-2. Prenatal ethanol exposure significantly decreased the NMDA receptor-mediated calcium entry compared to both pair-fed and ad libitum control groups. To determine the mechanisms of the prenatal ethanol exposure on the NMDA-mediated ion channel decrements, possible modulatory sites of the NMDA receptor were studied. Glycine (0.1, 1, 10 and 100 microM) increased calcium entry to an equal extent in the ethanol and control groups, but did not reverse the effect of prenatal ethanol exposure. Furthermore, low concentrations of MK801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5-10-imine hydrogen maleate] (25 and 50 nM) did not further inhibit calcium entry beyond that observed with the prenatal ethanol exposure, but significantly inhibited control group responses. Mg++ showed a similar result. With increasing concentrations of Mg++ the calcium entry in the three groups tended to converge. Thus, these results suggest that prenatal ethanol exposure inhibits the function of NMDA receptor-mediated ion channels by possibly altering the structural properties of the ion channel itself and/or by interacting with inner ion channel modulatory sites activated by Mg++ or MK801, and not the glycine site.