Kovács K J, Larson A A
Department of Veterinary PathoBiology, University of Minnesota, St. Paul 55108.
J Neurochem. 1994 Nov;63(5):1757-65. doi: 10.1046/j.1471-4159.1994.63051757.x.
Binding of 1-[1-(2-[3H]thienyl)cyclohexyl]piperidine ([3H]TCP) to mouse brain and spinal cord membranes was studied using compounds selective for the NMDA-coupled 1-(1-phenylcyclohexyl)piperidine (PCP) and/or sigma recognition sites. In both tissues, [3H]TCP labeled two populations of binding sites. Density of the low-affinity sites was approximately the same in both tissues, but the population of the high-affinity [3H]TCP sites was three times bigger in the brain than in the spinal cord. Self- and cross-displacement studies showed that the high-affinity [3H]TCP binding sites could be identical with NMDA receptor-coupled PCP sites, whereas the low-affinity [3H]TCP sites may be associated with sigma binding sites in both tissues. The NMDA-coupled PCP sites labeled in the presence of 6.25 nM [3H]TCP constituted a much higher percentage of the total binding in the brain (75%) than in the spinal cord (44%). Consistent with this, reintroduction of glycine and glutamate significantly increased, but DA antagonists significantly inhibited [3H]TCP binding in the brain but not in the spinal cord. Together, these data suggest that a large component of [3H]TCP-labeled binding sites in the spinal cord may be associated with sigma but not the NMDA receptor-coupled PCP sites.
使用对NMDA偶联的1-(1-苯基环己基)哌啶(PCP)和/或西格玛识别位点具有选择性的化合物，研究了1-[1-(2-[³H]噻吩基)环己基]哌啶([³H]TCP)与小鼠脑和脊髓膜的结合。在这两种组织中，[³H]TCP标记了两类结合位点。低亲和力位点的密度在两种组织中大致相同，但高亲和力[³H]TCP位点在脑中的数量是脊髓中的三倍。自身和交叉置换研究表明，高亲和力[³H]TCP结合位点可能与NMDA受体偶联的PCP位点相同，而低亲和力[³H]TCP位点可能与两种组织中的西格玛结合位点相关。在6.25 nM [³H]TCP存在下标记的NMDA偶联PCP位点在脑中占总结合的比例(75%)远高于脊髓(44%)。与此一致的是，重新引入甘氨酸和谷氨酸显著增加了，但多巴胺拮抗剂显著抑制了脑中的[³H]TCP结合，而对脊髓无此作用。总之，这些数据表明，脊髓中[³H]TCP标记的结合位点的很大一部分可能与西格玛相关，而与NMDA受体偶联的PCP位点无关。
