Quik M, Bordia T, Forno L, McIntosh J M
The Parkinson's Institute, Sunnyvale, California 94089, USA.
J Neurochem. 2004 Feb;88(3):668-79. doi: 10.1111/j.1471-4159.2004.02177.x.
Multiple nicotinic receptors are present in rodent and monkey striatum, with a selective localization of alpha-conotoxinMII-sensitive sites in the striatum and preferential declines in their numbers after nigrostriatal damage. Here we report the presence of 125I-alpha-conotoxinMII and alpha-conotoxinMII-sensitive 125I-epibatidine nicotinic receptors in human control and Parkinson's disease striatum. 125I-alpha-ConotoxinMII bound to control striatum with the characteristics of a nicotinic receptor ligand although the number of sites was approximately fivefold lower than in rodent and monkey. Competition analyses of alpha-conotoxinMII with 125I-epibatidine showed that toxin-sensitive sites comprised approximately 15% of nicotinic receptors in human striatum. In Parkinson's disease caudate, there was a approximately 50% decline in 125I-alpha-conotoxinMII sites with a similar decline in the dopamine transporter. In putamen, there were substantially greater losses of the dopamine transporter (80-90%) but only 50-60% decreases in 125I-alpha-conotoxinMII sites with corresponding declines in alpha-conotoxinMII-sensitive 125I-epibatidine sites, 125I-epibatidine (multiple) sites and 125I-A85380 (beta2-containing) nicotinic receptors. The greater loss of the transporter compared with nicotinic sites suggests that only a subpopulation of nicotinic receptors is located pre-synaptically on striatal dopaminergic neurons in man. Correlation analyses between changes in nicotinic receptors and the dopamine transporter in Parkinson's disease striatum suggest that alpha-conotoxinMII-sensitive 125I-epibatidine sites (low-affinity sites), 125I-A85380 and 125I-epibatidine sites are localized in part to dopaminergic terminals. In summary, these results show that alpha-conotoxinMII-sensitive sites are present in human striatum and that there are high- and low-affinity subtypes which are both decreased in Parkinson's disease.
啮齿动物和猴的纹状体中存在多种烟碱型受体，其中对α-芋螺毒素MII敏感的位点在纹状体中有选择性定位，并且在黑质纹状体损伤后其数量会优先减少。在此，我们报告在人类对照和帕金森病纹状体中存在125I-α-芋螺毒素MII以及对α-芋螺毒素MII敏感的125I-依博加碱烟碱型受体。125I-α-芋螺毒素MII与对照纹状体结合，具有烟碱型受体配体的特征，尽管其位点数量比啮齿动物和猴的约低五倍。α-芋螺毒素MII与125I-依博加碱的竞争分析表明，毒素敏感位点约占人类纹状体中烟碱型受体的15%。在帕金森病尾状核中，125I-α-芋螺毒素MII位点减少约50%，多巴胺转运体也有类似程度的减少。在壳核中，多巴胺转运体的损失更大（80 - 90%），但125I-α-芋螺毒素MII位点仅减少50 - 60%，同时对α-芋螺毒素MII敏感的125I-依博加碱位点、125I-依博加碱（多个）位点和125I-A85380（含β2）烟碱型受体也相应减少。与烟碱型位点相比，转运体损失更大，这表明在人类中，只有一部分烟碱型受体位于纹状体多巴胺能神经元的突触前。帕金森病纹状体中烟碱型受体变化与多巴胺转运体变化之间的相关性分析表明，对α-芋螺毒素MII敏感的125I-依博加碱位点（低亲和力位点）、125I-A85380和125I-依博加碱位点部分定位于多巴胺能终末。总之，这些结果表明人类纹状体中存在对α-芋螺毒素MII敏感的位点，并且存在高亲和力和低亲和力亚型，在帕金森病中两者均减少。
