Miyoshi R, Kito S, Doudou N, Nomoto T
Department of Pharmacology, Tokyo Women's Medical College, Japan.
Synapse. 1991 Jul;8(3):212-7. doi: 10.1002/syn.890080307.
The N-methyl-D-aspartate (NMDA) receptor complex has been considered to consist of an L-glutamate recognition site, a strychnine-insensitive glycine modulatory site, and a voltage-dependent cation channel. In this study, an effect of age on NMDA antagonist binding sites was investigated through quantitative in vitro autoradiography with 3H-3-((+)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP). 3H-CPP binding sites were most concentrated in the hippocampus and cerebral cortex where NMDA receptors have been demonstrated to be involved in synaptic transmission. In aged rats, 3H-CPP binding sites in the hippocampus and cerebral cortex were not significantly changed. As for other brain regions, there was an age-dependent decline of binding sites only in the caudate-putamen and nucleus accumbens. Our previous study revealed that strychnine-insensitive glycine receptors were markedly reduced in telencephalic regions in the aged rat brain. Taking these findings into consideration, it is concluded that glycine receptors but not NMDA antagonist binding sites are severely altered in telencephalic regions of aged animals. It is considered that within the NMDA receptor complex, glycine receptors may be selectively affected in the aging process.
N-甲基-D-天冬氨酸（NMDA）受体复合物被认为由一个L-谷氨酸识别位点、一个对士的宁不敏感的甘氨酸调节位点和一个电压依赖性阳离子通道组成。在本研究中，通过使用3H-3-（（+）-2-羧基哌嗪-4-基）丙基-1-膦酸（CPP）进行定量体外放射自显影，研究了年龄对NMDA拮抗剂结合位点的影响。3H-CPP结合位点最集中在海马体和大脑皮层，在这些部位已证实NMDA受体参与突触传递。在老年大鼠中，海马体和大脑皮层中的3H-CPP结合位点没有显著变化。至于其他脑区，仅在尾状核-壳核和伏隔核中存在结合位点的年龄依赖性下降。我们之前的研究表明，在老年大鼠脑的端脑区域，对士的宁不敏感的甘氨酸受体显著减少。考虑到这些发现，可以得出结论，在老年动物的端脑区域，甘氨酸受体而非NMDA拮抗剂结合位点发生了严重改变。据认为，在NMDA受体复合物中，甘氨酸受体可能在衰老过程中受到选择性影响。
