Zhang L, Zheng X, Paupard M C, Wang A P, Santchi L, Friedman L K, Zukin R S, Bennett M V
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461.
Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):10883-7. doi: 10.1073/pnas.91.23.10883.
The present study shows that both the NR1 and NR2 subunits critically affect spermine potentiation of heteromeric recombinant N-methyl-D-aspartate receptors. NR1(011), the most prominent NR1 splice variant in rat forebrain, and NR1(100), prominent in midbrain, were expressed in Xenopus oocytes singly and in combination with NR2A, NR2B, and NR2C subunits. As for NR1(011) homomers, NR1(011)/NR2B receptors exhibited spermine potentiation by two mechanisms: by increasing glycine affinity and by increasing current through receptors with bound N-methyl-D-aspartate and glycine. NR1(011)/NR2A receptors exhibited only the increase in glycine affinity, and NR1(011)/NR2C receptors exhibited neither. As for NR1(100) homomers, NR1(100)/NR2B and NR1(100)/NR2A receptors exhibited spermine potentiation only by increasing the glycine affinity. Spermine produced no potentiation of NR1(100)/NR2C receptors. Thus, the NR2B subunit "permits" both forms of spermine potentiation, the NR2A subunit permits spermine potentiation only by increasing the glycine affinity, and th NR2C subunit permits neither form of potentiation. Spermine actions on NR1/NR2 showed little voltage dependence. These observations are of interest because the NR1 and NR2 subunits are differentially distributed and developmentally regulated. At early postnatal ages, NR2B subunit mRNA was more highly expressed than NR2A and NR2C mRNAs in hippocampus, neocortex, and caudate-putamen. These findings account for many of the observed differences among neurons in polyamine actions and suggest that these actions will vary in a cell-specific and age-related manner.
本研究表明，NR1和NR2亚基均对异聚体重组N-甲基-D-天冬氨酸受体的精胺增强作用产生关键影响。NR1(011)是大鼠前脑中最主要的NR1剪接变体，而NR1(100)在中脑中较为突出，它们分别单独以及与NR2A、NR2B和NR2C亚基组合在非洲爪蟾卵母细胞中表达。对于NR1(011)同聚体，NR1(011)/NR2B受体通过两种机制表现出精胺增强作用：通过增加甘氨酸亲和力以及通过增加与结合了N-甲基-D-天冬氨酸和甘氨酸受体的电流。NR1(011)/NR2A受体仅表现出甘氨酸亲和力增加，而NR1(011)/NR2C受体则两者均未表现。对于NR1(100)同聚体而言，NR1(100)/NR2B和NR1(100)/NR2A受体仅通过增加甘氨酸亲和力表现出精胺增强作用。精胺对NR1(100)/NR2C受体没有增强作用。因此，NR2B亚基“允许”两种形式的精胺增强作用，NR2A亚基仅通过增加甘氨酸亲和力允许精胺增强作用，而NR2C亚基则不允许任何一种增强形式。精胺对NR1/NR2受体的作用几乎没有电压依赖性。这些观察结果很有趣，因为NR1和NR2亚基分布不同且受发育调控。在出生后早期阶段，海马体、新皮层以及尾状核-壳核中NR2B亚基mRNA比NR2A和NR2C mRNA表达水平更高这些发现解释了多胺作用中神经元间许多已观察到的差异，并表明这些作用将以细胞特异性和年龄相关的方式变化。
