Striatal binding of 2-amino-6,7-[3H]dihydroxy-1,2,3,4- tetrahydronaphthalene to two dopaminergic sites distinguished by their low and high affinity for neuroleptics
Striatal binding of 2-amino-6,7-[3H]dihydroxy-1,2,3,4- tetrahydronaphthalene to two dopaminergic sites distinguished by their low and high affinity for neuroleptics
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2-氨基-6,7-[3H]二羟基-1,2,3,4-四氢萘的纹状体与两个多巴胺能位点的结合，其特征在于对精神安定药的低亲和力和高亲和力
DOI：
10.1523/jneurosci.02-07-00895.1982
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发表时间：
1982
期刊：
影响因子：
6.1
通讯作者：
P. Seeman
中科院分区：
文献类型：
--
作者：
S. List;K. Wreggett;P. Seeman
为了开发更具选择性的脑多巴胺受体标记方法，本研究详细描述了2-氨基- 6,7，-[3H]二羟基-1,2,3,4，-四氢萘（[3H] ADTN）在大鼠、小牛和人脑中与多巴胺能位点结合的特性。[3H]ADTN在大鼠、小牛和人的大脑纹状体中标记了两种不同类型的多巴胺能结合位点。极低浓度的多巴胺和多巴胺能儿茶酚胺（IC50值为1 ~ 10 nM）抑制了[3H]ADTN与这两个位点的结合。然而，神经阻滞剂在两个截然不同的浓度范围内抑制[3H]ADTN的结合，其中一个位点的IC50值为0.15至40 nM，另一个位点的IC50值为100至50,000 nM。对多巴胺高亲和力和对抗精神病药物低亲和力的位点具有与先前表征的D3位点相对应的结合特性（List， S.， M. Titeler, and P. Seeman (1980) Biochem）。药理学杂志，29:1621 - 1622)。[3H]ADTN与神经抑制药高亲和力的结合位点表现出与3H-神经抑制药标记位点相似的结合特征（Sokoloff， P., m.p. Martres, and J. C. Schwartz(1980)）。医学杂志，31(3):89-102。[3H]阿波啡似乎将相同的两个位点标记为[3H]ADTN，而[3H]多巴胺只标记D3位点。在选择性标记抗精神病药低亲和力位点（D3）和高亲和力位点的条件下，对[3H]ADTN或[3H]阿波啡结合进行Scatchard分析，检测到每种蛋白的密度为70 fmol/mg。小牛纹状体中D3位点的密度（170 fmol/mg蛋白）远大于高亲和力抗精神病药位点（50 fmol/mg蛋白）。在大鼠体内，[3H]ADTN在两个位点的解离常数（KD）均为2 nM。[3H]阿波啡对D3位点的亲和力（KD=1.6 nM）高于对高亲和力抗精神病药位点的亲和力（KD=4.2 nM）。目前的结果可以解释先前观察到的[3H]ADTN， [3H]阿波啡和[3H]多巴胺结合之间的物种和实验室差异。
In order to develop more selective methods for labeling brain dopamine receptors, this study describes in detail the properties of 2-amino- 6,7,-[3H]dihydroxy-1,2,3,4,-tetrahydronaphthalene ([3H] ADTN) binding to dopaminergic sites in rat, calf, and human brain. [3H]ADTN labeled two distinct types of dopaminergic binding sites in the brain striatum of the rat, calf, and human. Very low concentrations of dopamine and dopaminergic catecholamines (with IC50 values of 1 to 10 nM) inhibited the binding of [3H]ADTN to both sites. Neuroleptics, however, inhibited the binding of [3H]ADTN in two distinctly separate concentration ranges, with IC50 values of 0.15 to 40 nM at one site and 100 and 50,000 nM at the other site. The site with high affinity for dopamine and low affinity for neuroleptics had binding properties that corresponded to those of the previously characterized D3 site (List, S., M. Titeler, and P. Seeman (1980) Biochem. Pharmacol. 29: 1621– 1622). The [3H]ADTN binding site with high affinity for neuroleptics demonstrated binding characteristics similar to a site labeled by 3H- Neuroleptics (Sokoloff, P., M. P. Martres, and J. C. Schwartz (1980) Naunyn Schmiedebergs Arch. Pharmacol. 315: 89–102). [3H]Apomorphine appeared to label the same two sites as [3H]ADTN, while [3H]dopamine labeled only the D3 site. Scatchard analysis of [3H]ADTN or [3H]apomorphine binding, under conditions for selective labeling of the low affinity neuroleptic site (D3) and the high affinity site for neuroleptics, detected a density of 70 fmol/mg of protein for each. The density of the D3 site in the calf striatum (170 fmol/mg of protein) was much greater than that of the high affinity neuroleptic site (50 fmol/mg). In the rat, the dissociation constant (KD) of [3H]ADTN was 2 nM for both sites. [3H]Apomorphine, however, had a higher affinity for the D3 site (KD=1.6 nM) than for the high affinity neuroleptic site (KD=4.2 nM). The present results may explain previously observed species and laboratory differences between the binding of [3H]ADTN, [3H]apomorphine, and [3H]dopamine.