Maloteaux J M, Vanisberg M A, Laterre C, Javoy-Agid F, Agid Y, Laduron P M
Laboratoire de Neurochimie, Université Catholique de Louvain, Brussels, Belgium.
Eur J Pharmacol. 1988 Nov 8;156(3):331-40. doi: 10.1016/0014-2999(88)90278-6.
[3H]GBR 12935 bound with high affinity to dopamine uptake sites in rat striatum where a close parallelism was observed between the subcellular localization profiles for [3H]dopamine uptake and [3H]GBR 12935 specific binding. Using the same ligand, we characterized the dopamine uptake sites in human striatum: the mean KD value was 3.2 nM and the specific binding was inhibited by several dopamine uptake blockers but with slightly lower affinities than those observed in the rat. The subcellular localization profile revealed a synaptosomal enrichment of the specific binding in human striatum. [3H]GBR 12935 binding was decreased in the putamen and caudate nucleus of subjects with Parkinson's disease (33 and 46% of control values, respectively) and progressive supranuclear palsy (38 and 57% of control values, respectively). It is very unlikely that the remaining binding sites in both diseases correspond to piperazine acceptor sites that are not involved in dopamine uptake. However, we cannot exclude the possibility that some of these remaining dopamine transporter sites are not functional, since the reduction in [3H]GBR 12935 specific binding was less marked than the decrease in the dopamine content of the same areas.
[3H]GBR 12935与大鼠纹状体中的多巴胺摄取位点具有高亲和力结合，在该部位观察到[3H]多巴胺摄取和[3H]GBR 12935特异性结合的亚细胞定位图谱之间存在密切的平行关系。使用相同的配体，我们对人纹状体中的多巴胺摄取位点进行了表征：平均KD值为3.2 nM，特异性结合受到几种多巴胺摄取阻滞剂的抑制，但亲和力略低于在大鼠中观察到的亲和力。亚细胞定位图谱显示人纹状体中特异性结合在突触体中富集。在帕金森病患者的壳核和尾状核中，[3H]GBR 12935结合减少（分别为对照值的33%和46%），在进行性核上性麻痹患者中也减少（分别为对照值的38%和57%）。在这两种疾病中，剩余的结合位点极不可能对应于不参与多巴胺摄取的哌嗪受体位点。然而，我们不能排除这些剩余的多巴胺转运体位点中有些没有功能的可能性，因为[3H]GBR 12935特异性结合的减少不如同一区域多巴胺含量的减少明显。
