SEVERE DEPLETION OF COCAINE RECOGNITION SITES ASSOCIATED WITH THE DOPAMINE TRANSPORTER IN PARKINSONS-DISEASED STRIATUM
SEVERE DEPLETION OF COCAINE RECOGNITION SITES ASSOCIATED WITH THE DOPAMINE TRANSPORTER IN PARKINSONS-DISEASED STRIATUM
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DOI：
10.1002/syn.890090107
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发表时间：
1991-09-01
期刊：
影响因子：
2.3
通讯作者：
MADRAS, BK
中科院分区：
文献类型：
--
作者：
KAUFMAN, MJ;MADRAS, BK
可卡因同系物[H-3]CFT，也称为[H-3]WIN 35，428（2-β-甲氧羰基-3-β-（4-氟苯基托烷），标记与灵长类纹状体中多巴胺转运蛋白相关的可卡因受体。比较了人死后对照和帕金森病患者纹状体组织切片中[H-3]CFT结合（5 nM）的放射自显影分布。在对照组织中，在壳核和尾状核中观察到高水平和相当水平的[H-3]CFT结合。至少90-99%的总[H-3]CFT结合被（-）-可卡因（30 μ M）抑制，表明高比例的[H-3]CFT被特异性结合。在帕金森病组织中，[H-3]CFT的结合位点在尾状核中减少了80%，在壳核中减少了96%。这种消耗模式与先前报道的这些脑区域中多巴胺的损失相似（Kish，Shannak和Hornykiewicz，New Engl. J. Med.，318：876-880，1988）。在帕金森病组织的背侧尾状核中，观察到[H-3]CFT结合的外侧到内侧梯度，外侧尾状核比内侧尾状核更严重地耗尽。帕金森病患者纹状体中[H-3]CFT结合位点的显着减少支持了以下结论：1）多巴胺转运蛋白主要定位于突触前黑质纹状体末端; 2）在尾状核和壳核中，可卡因识别位点主要与多巴胺转运蛋白相关; 3）[H-3]CFT的非特异性结合水平低，[H-3] CFT标记位点明显减少，提示CFT的放射性标记衍生物或其同类物可能是突触前多巴胺神经末梢的合适显像探针。
The cocaine congener [H-3]CFT, also designated [H-3]WIN 35,428 (2-beta-carbomethoxy-3-beta-(4-fluorophenyltropane), labels cocaine receptors associated with the dopamine transporter in primate striatum. Autoradiographic distribution of [H-3]CFT binding (5 nM) in human postmortem control and Parkinson's-diseased striatal tissue sections was compared. In control tissue, high and comparable levels of [H-3]CFT binding were observed in the putamen and caudate nucleus. At least 90-99% of total [H-3]CFT bound was inhibited by (-)-cocaine (30-mu-M), suggesting that a high proportion of [H-3]CFT is specifically bound. In Parkinson's-diseased tissue, binding sites for [H-3]CFT were reduced by 80% in the caudate nucleus and 96% in the putamen. This pattern of depletion parallels the previously reported loss of dopamine in these brain regions (Kish, Shannak, and Hornykiewicz, New Engl. J. Med., 318:876-880, 1988). In the dorsal caudate nucleus of Parkinson's-diseased tissue, a lateral-to-medial gradient of [H-3]CFT binding was observed, with the lateral caudate more severely depleted than the medial caudate. The marked decrease of [H-3]CFT binding sites in Parkinson's diseased striatum supports the following conclusions: 1) the dopamine transporter is localized primarily on presynaptic nigrostriatal terminals; 2) in the caudate and putamen, cocaine recognition sites are associated primarily with the dopamine transporter; 3) the low level of nonspecific binding of [H-3]CFT and the marked depletion of [H-3]CFT-labeled sites suggest that radiolabeled derivatives of CFT or its congeners may be suitable imaging probes for presynaptic dopamine nerve terminals.