Steele J E, Robinson T N, Cross A J, Bowen D M, Green A R
Department of Neurochemistry, Institute of Neurology, London, England.
J Neurochem. 1991 Apr;56(4):1248-54. doi: 10.1111/j.1471-4159.1991.tb11418.x.
The binding of (+)-[3H]5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine maleate ([3H]MK-801) and N-[1-(2-thienyl)cyclohexyl]-3,4-[3H]piperidine ([3H]TCP) to the N-methyl-D-aspartate (NMDA) receptor complex of human brain has been investigated. Significant differences were noted between the binding of the two ligands in the same tissue samples. Binding of both ligands was stimulated by addition of glutamic acid or glycine. However, addition of both compounds resulted in an additional effect with [3H]MK-801 but not [3H]TCP binding. Saturation analysis revealed approximately twice as many high-affinity sites for [3H]MK-801 (Bmax, 1,500 +/- 300 fmol/mg of protein) than for [3H]TCP (Bmax, 660 +/- 170 fmol/mg of protein). In addition, a low-affinity site was detected for [3H]MK-801 binding but not [3H]TCP binding. The pharmacology of the high-affinity [3H]MK-801 and [3H]TCP binding sites was similar with rank order of potency of inhibitors being MK801 greater than TCP greater than phencyclidine greater than N-allylnormetazocine (SKF 10047). 2-Amino-5-phosphonopentanoate inhibited binding of both ligands with comparable potency whereas both 7-chlorokynurenic acid and ZnCl2 were more potent inhibitors of [3H]MK-801 than of [3H]TCP binding. All compounds examined exhibited Hill coefficients of significantly less than unity. Saturation analysis performed in the striatum revealed that the number of binding sites was the same for both [3H]MK-801 (Bmax, 1,403 +/- 394 fmol/mg) and [3H]TCP (Bmax, 1,292 +/- 305 fmol/mg). Addition of glutamate or glycine stimulated striatal binding but there was no further increase on addition of both together.(ABSTRACT TRUNCATED AT 250 WORDS)
研究了（+）-[3H]5-甲基-10,11-二氢-5H-二苯并[a,d]环庚烯-5,10-亚胺马来酸盐（[3H]MK-801）和N-[1-（2-噻吩基）环己基]-3,4-[3H]哌啶（[3H]TCP）与人脑N-甲基-D-天冬氨酸（NMDA）受体复合物的结合情况。在相同组织样本中，两种配体的结合存在显著差异。谷氨酸或甘氨酸的添加会刺激两种配体的结合。然而，两种化合物的添加对[3H]MK-801的结合产生了额外影响，对[3H]TCP的结合则没有。饱和分析显示，[3H]MK-801的高亲和力位点数量（Bmax，1500±300 fmol/mg蛋白质）约为[3H]TCP（Bmax，660±170 fmol/mg蛋白质）的两倍。此外，检测到[3H]MK-801存在低亲和力位点，而[3H]TCP不存在。高亲和力[3H]MK-801和[3H]TCP结合位点的药理学性质相似，抑制剂的效力顺序为MK801＞TCP＞苯环利定＞N-烯丙基去甲左啡诺（SKF 10047）。2-氨基-5-膦酰戊酸以相当的效力抑制两种配体的结合，而7-氯犬尿氨酸和ZnCl2对[3H]MK-801结合的抑制作用比对[3H]TCP结合更强。所有检测的化合物的希尔系数均显著小于1。在纹状体中进行的饱和分析表明，[3H]MK-801（Bmax，1403±394 fmol/mg）和[3H]TCP（Bmax，1292±305 fmol/mg）的结合位点数量相同。谷氨酸或甘氨酸的添加刺激了纹状体结合，但两者同时添加时没有进一步增加。（摘要截短至250字）
