Aicher S A, Sharma S, Cheng P Y, Pickel V M
Department of Neurology and Neuroscience, Cornell University Medical College, New York, NY 10021, USA.
Brain Res. 1997 Oct 24;772(1-2):71-81. doi: 10.1016/s0006-8993(97)00637-9.
The N-methyl-D-aspartate (NMDA) receptor is thought to mediate the postsynaptic effects of excitatory amino acids released from primary afferent terminals in the superficial layers of the dorsal horn of the spinal cord where synergistic associations with substance P (SP) have been implicated in the production of hyperalgesia. We examined the electron microscopic dual immunocytochemical localization of SP and the R1 subunit of the NMDA receptor (NMDAR1) in this region to determine the cellular basis for interactions between SP and NMDA receptor ligands. Of 971 profiles immunolabeled for NMDAR1, 40% were dendrites and the remainder were primarily unmyelinated axons and astrocytic processes. In dendrites, NMDAR1-like immunoreactivity (NMDAR1-LI) was associated with synaptic and non-synaptic portions of the plasma membrane, as well as intracellular membranes including smooth endoplasmic reticulum. These NMDAR1-labeled dendrites received synaptic input from unlabeled terminals and from terminals containing SP and/or NMDAR1-LI and they occasionally (25/389) also contained SP. In contrast, of 540 SP-immunoreactive profiles, 60% were axon terminals and the majority (252/324) of these SP-labeled terminals were presynaptic to NMDAR1-containing dendrites. These results provide anatomical evidence that the synergistic nociceptive effects of SP and NMDA ligands are attributed mainly to dual modulation of the activity of single dendritic targets in the dorsal horn of the spinal cord. They also suggest that activation of NMDA receptors may also play a role in the modulation of SP neurons, presynaptic release of SP or other neurotransmitters, and in glial function in the dorsal horn.
N-甲基-D-天冬氨酸（NMDA）受体被认为介导了脊髓背角浅层初级传入终末释放的兴奋性氨基酸的突触后效应，其中与P物质（SP）的协同作用被认为与痛觉过敏的产生有关。我们检查了该区域中SP和NMDA受体R1亚基（NMDAR1）的电子显微镜双免疫细胞化学定位，以确定SP与NMDA受体配体之间相互作用的细胞基础。在971个被免疫标记为NMDAR1的细胞轮廓中，40%是树突，其余主要是无髓轴突和星形胶质细胞突起。在树突中，NMDAR1样免疫反应性（NMDAR1-LI）与质膜的突触和非突触部分以及包括光滑内质网在内的细胞内膜相关。这些被NMDAR1标记的树突接受来自未标记终末以及含有SP和/或NMDAR1-LI的终末的突触输入，并且它们偶尔（25/389）也含有SP。相比之下，在540个SP免疫反应性细胞轮廓中，60%是轴突终末，并且这些被SP标记的终末中的大多数（252/324）在含NMDAR1的树突之前形成突触。这些结果提供了解剖学证据，表明SP和NMDA配体的协同伤害感受效应主要归因于对脊髓背角单个树突靶点活性的双重调节。它们还表明，NMDA受体的激活可能也在SP神经元的调节、SP或其他神经递质的突触前释放以及背角神经胶质细胞功能中发挥作用。
