NAAG reduces NMDA receptor current in CA1 hippocampal pyramidal neurons of acute slices and dissociated neurons
NAAG reduces NMDA receptor current in CA1 hippocampal pyramidal neurons of acute slices and dissociated neurons
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DOI：
10.1038/sj.npp.1300559
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发表时间：
2005-01-01
影响因子：
7.6
通讯作者：
Greene, RW
中科院分区：
文献类型：
--
作者：
Bergeron, R;Coyle, JT;Greene, RW
N-乙酰天冬氨酸(NAAG)是神经系统中含量丰富的神经肽，但其功能尚不清楚。采用全细胞膜片钳技术记录急性制备的海马脑片CA1区锥体神经元。在低浓度(20um)时，NAAG可降低N-甲基-D-天冬氨酸受体(NMDAR)介导的突触电流或NMDA诱导的电流。NAAG诱导的NMDA浓度/反应曲线的变化表明，这种拮抗作用不是竞争性的。然而，NAAG引起的NMDAR共激动剂甘氨酸的浓度/反应曲线的变化表明，甘氨酸可以克服NAAG的拮抗作用。在高效选择性mGluR3拮抗剂LY-341495存在下，NAAG诱导的NMDAR仍有拮抗作用。此外，在分离的CA1区锥体神经元上，NAAG也降低了NMDA电流，这一作用可被甘氨酸逆转。这些结果表明，NAAG降低了海马CA1区锥体神经元的NMDA电流。
N-Acetylaspartylglutamate (NAAG) is an abundant neuropeptide in the nervous system, yet its functions are not well understood. Pyramidal neurons of the CA1 sector of acutely prepared hippocampal slices were recorded using the whole-cell patch-clamp technique. At low concentrations (20 muM), NAAG reduced isolated N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic currents or NMDA-induced currents. The NAAG-induced change in the NMDA concentration/response curve suggested that the antagonism was not competitive. However, the NAAG-induced change in the concentration/response curve for the NMDAR co-agonist, glycine, indicated that glycine can overcome the NAAG antagonism. The antagonism of the NMDAR induced by NAAG was still observed in the presence of LY-341495, a potent and selective mGluR3 antagonist. Moreover, in dissociated pyramidal neurons of the CA1 region, NAAG also reduced the NMDA current and this effect was reversed by glycine. These results suggest that NAAG reduces the NMDA currents in hippocampal CA1 pyramidal neurons.