Sakurai S Y, Penney J B, Young A B
Department of Neurology, University of Michigan, Ann Arbor.
J Neurochem. 1993 Apr;60(4):1344-53. doi: 10.1111/j.1471-4159.1993.tb03295.x.
Quantitative autoradiography of [3H]MK-801 binding was used to characterize regional differences in N-methyl-D-aspartate (NMDA) receptor pharmacology in rat CNS. Regionally distinct populations of NMDA receptors were distinguished on the basis of regulation of [3H]MK-801 binding by the NMDA antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP). CPP inhibited [3H]MK-801 binding in outer cortex (OC) and medial cortex (MC) with apparent Ki values of 0.32-0.48 microM, whereas in the medial striatum (MS), lateral striatum (LS), CA1, and dentate gyrus (DG) of hippocampus, apparent Ki values were 1.1-1.6 microM. In medial thalamus (MT) and lateral thalamus (LT) the apparent Ki values were 0.78 microM. In the presence of added glutamate (3 microM), the relative differences in apparent Ki values between regions maintained a similar relationship with the exception of the OC. Inhibition of [3H]MK-801 binding by the glycine site antagonist 7-chlorokynurenic acid (7-ClKyn) distinguished at least two populations of NMDA receptors that differed from populations defined by CPP displacement. 7-ClKyn inhibited [3H]MK-801 binding in OC, MC, MS, and LS with apparent Ki values of 6.3-8.6 microM, whereas in CA1, DG, LT, and MT, Ki values were 11.4-13.6 microM. In the presence of added glycine (1 microM), the relative differences in apparent Ki values were maintained. Under conditions of differential receptor activation, regional differences in NMDA receptor pharmacology can be detected using [3H]MK-801 binding.
采用[3H]MK-801结合的定量放射自显影技术来表征大鼠中枢神经系统中N-甲基-D-天冬氨酸（NMDA）受体药理学的区域差异。基于NMDA拮抗剂3-(2-羧基哌嗪-4-基)-丙基-1-膦酸（CPP）对[3H]MK-801结合的调节作用，区分出了区域特异性的NMDA受体群体。CPP抑制大脑外层皮质（OC）和内侧皮质（MC）中[3H]MK-801的结合，其表观解离常数（Ki）值为0.32 - 0.48微摩尔，而在海马体的内侧纹状体（MS）、外侧纹状体（LS）、CA1区和齿状回（DG）中，表观Ki值为1.1 - 1.6微摩尔。在内侧丘脑（MT）和外侧丘脑（LT）中，表观Ki值为0.78微摩尔。在添加谷氨酸（3微摩尔）的情况下，除了OC区，各区域之间表观Ki值的相对差异保持相似关系。甘氨酸位点拮抗剂7-氯犬尿氨酸（7-ClKyn）对[3H]MK-801结合的抑制作用区分出了至少两个与CPP置换所定义的群体不同的NMDA受体群体。7-ClKyn抑制OC、MC、MS和LS中[3H]MK-801的结合，其表观Ki值为6.3 - 8.6微摩尔，而在CA1区、DG区、LT区和MT区，Ki值为11.4 - 13.6微摩尔。在添加甘氨酸（1微摩尔）的情况下，表观Ki值的相对差异得以保持。在受体激活不同的条件下，使用[3H]MK-801结合可检测到NMDA受体药理学的区域差异。
