APPLICATIONS OF QUANTITATIVE MEASUREMENTS FOR ASSESSING GLUTAMATE NEUROTOXICITY

APPLICATIONS OF QUANTITATIVE MEASUREMENTS FOR ASSESSING GLUTAMATE NEUROTOXICITY
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DOI:
10.1073/pnas.85.11.4071
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发表时间:
1988-06-01
影响因子:
11.1
通讯作者:
STEVENS, CF
STEVENS, CF
中科院分区:
综合性期刊1区
文献类型:
--
作者:
FINKBEINER, S;STEVENS, CF

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在培养的海马CA 1区神经元中研究了N-甲基-D-天冬氨酸受体通道在谷氨酸神经毒性中的作用。一个方程,生存函数,被开发来量化神经毒性的推定调节剂的影响。2-氨基-5-膦酰基戊酸(30 μ M)将神经元对谷氨酸的敏感性降低了20倍以上,而甘氨酸(1 μ M)将其增强了7.5 ± 1倍。2.5.基于Mg 2+阻断N-甲基-D-天冬氨酸通道的能力,以可预测的方式通过增加Mg 2+浓度来保护神经元。这些研究结果提供了一个定量的基础,评估各种神经保护剂,并进一步支持的假设,N-甲基-D-天冬氨酸通道是中央谷氨酸神经毒性。
The role of the N-methyl-D-aspartate receptor channel in glutamate neurotoxicity was investigated in cultured hippocampal neurons of the CA1 region. An equation, the survival function, was developed to quantify the effects of putative modulators of neurotoxicity. 2-Amino-5-phosphonovaleric acid (30 .mu.M) reduced the neuronal sensitivity to glutamate by a factor > 20, whereas glycine (1 .mu.M) enhanced it by a factor of 7.5 .+-. 2.5. Neurons were protected by increasing Mg2+ concentrations in a predictable way based on the ion''s ability to block the N-methyl-D-aspartate channel. These findings provide a quantitative basis for the assessment of various neuroprotective agents and add further support to the hypothesis that the N-methyl-D-aspartate channel is central to glutamate neurotoxicity.