Maragos W F, Greenamyre J T, Chu D C, Penney J B, Young A B
Department of Neurology, University of Michigan, Ann Arbor 48104.
Brain Res. 1991 Jan 4;538(1):36-45. doi: 10.1016/0006-8993(91)90373-4.
The neuronal localization of glutamate and phencyclidine (PCP) receptors was evaluated in the cerebral cortex and hippocampal formation of rat CNS using quantitative autoradiography. Scatchard analysis of [3H]glutamate binding in the cortex (layers I and II and V and VI) showed no difference in the total number of binding sites (Bmax) or apparent affinity (Kd) 1 week, 1 month and 2 months following unilateral ibotenate lesions to nucleus basalis of Meynert (nbM) compared to the non-lesioned side. Quisqualic acid displacement of [3H]glutamate in layers I and II, 1 week following nbM destruction, revealed both high- and low-affinity binding sites (representing the quisqualate (QA) and N-methyl-D-aspartate (NMDA) sites, respectively). Compared to the control side, there was no difference in binding parameters for either of the receptor sites. In similarly lesioned animals, the NMDA receptor was specifically labelled with [3H]glutamate and the associated PCP receptor labelled with [3H]N-(1-[2-thienyl]cyclohexyl)3,4-piperidine ([3H]TCP) in adjacent brain sections. For both receptors, there was no change in the total number of binding sites in the cortex following destruction of nbM. On the other hand, virtually all binding to NMDA and PCP receptors was eliminated following chemical destruction of intrinsic cortical neurons. These results suggest that the NMDA/PCP receptor complex does not exist on the terminals of cortical cholinergic afferents. One week after knife cuts of the glutamatergic entorhinal pathway to the hippocampal formation only an approximate 10% reduction of NMDA and PCP receptors was seen in the dentate gyrus. Conversely, selective destruction of the dentate granule cells using colchicine caused a near identical loss of NMDA and PCP receptors (84% vs 92% respectively). It is concluded from these experiments that glutamate and PCP receptors exist almost exclusively on neurons intrinsic to the hippocampal formation and that no more than 10% of NMDA and PCP receptors exist as autoreceptors on glutamatergic terminals.
利用定量放射自显影技术，在大鼠中枢神经系统的大脑皮层和海马结构中评估了谷氨酸和苯环己哌啶（PCP）受体的神经元定位。对大脑皮层（I层、II层、V层和VI层）中[3H]谷氨酸结合进行Scatchard分析，结果显示，与未损伤侧相比，在单侧鹅膏蕈氨酸损伤Meynert基底核（nbM）1周、1个月和2个月后，结合位点总数（Bmax）或表观亲和力（Kd）均无差异。在nbM破坏1周后，I层和II层中[3H]谷氨酸的quisqualic酸置换显示出高亲和力和低亲和力结合位点（分别代表quisqualate（QA）和N-甲基-D-天冬氨酸（NMDA）位点）。与对照侧相比，任一受体位点的结合参数均无差异。在同样受损的动物中，相邻脑切片中NMDA受体用[3H]谷氨酸特异性标记，相关的PCP受体用[3H]N-（1-[2-噻吩基]环己基）3,4-哌啶（[3H]TCP）标记。对于这两种受体，nbM破坏后大脑皮层中结合位点总数均无变化。另一方面，在化学破坏内源性皮层神经元后，几乎所有与NMDA和PCP受体的结合都被消除。这些结果表明，NMDA/PCP受体复合物不存在于皮层胆碱能传入神经的终末。在谷氨酸能内嗅通路切断至海马结构1周后，齿状回中仅观察到NMDA和PCP受体减少约10%。相反，使用秋水仙碱选择性破坏齿状颗粒细胞导致NMDA和PCP受体几乎相同程度的丢失（分别为84%和92%）。从这些实验得出的结论是，谷氨酸和PCP受体几乎只存在于海马结构的内源性神经元上，并且不超过10%的NMDA和PCP受体作为谷氨酸能终末上的自身受体存在。
