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帕金森病大脑中多巴的脱羧作用:在动物模型上的体内研究

The decarboxylation of DOPA in the parkinsonian brain: in vivo studies on an animal model.

作者信息

Hefti F, Melamed E, Wurtman R J

出版信息

J Neural Transm Suppl. 1980(16):95-101. doi: 10.1007/978-3-7091-8582-7_10.

DOI:10.1007/978-3-7091-8582-7_10
PMID:6776238
Abstract

The site of decarboxylation of exogenously administered L-DOPA was studied in corpora striata of rats with near-total unilateral nigrostriatal lesions. After DOPA administration, the absolute increases in dopamine (DA) levels were lower in lesioned than in unlesioned striata, suggesting that, in the intact striatum, a major part of exogenous DOPA is decarboxylated in DA neurons. DOPA can also be decarboxylated outside DA neurons, however, as shown by our finding that relatively higher DOPA decarboxylase than tyrosine hydroxylase activity or DA concentration remains in striata after the nigrostriatal lesions. Also, the percentage increases in DA formation after DOPA administration were much higher in lesioned than in control striata. Rats with both raphé and nigrostriatal lesions failed to exhibit further reductions in striatal DOPA decarboxylase activity or diminished biochemical or behavioral (turning behavior) reactions to DOPA. Inhibition of the DOPA decarboxylase contained in brain capillary endothelial cells did not abolish DA formation in lesioned striata or circling behavior after DOPA administration. These findings all suggest an additional cell type in the striatum as the site of DOPA's decarboxylation in the absence of DA neurons.

摘要

在几乎完全单侧黑质纹状体损伤的大鼠纹状体内,研究了外源性给予左旋多巴(L-DOPA)的脱羧部位。给予多巴后,损伤侧纹状体中多巴胺(DA)水平的绝对增加值低于未损伤侧,这表明在完整的纹状体中,外源性多巴的大部分在多巴胺能神经元中脱羧。然而,多巴也可以在多巴胺能神经元外脱羧,正如我们的研究所显示的,黑质纹状体损伤后,纹状体中多巴脱羧酶的活性相对高于酪氨酸羟化酶活性或多巴胺浓度。此外,给予多巴后,损伤侧纹状体中多巴胺生成的百分比增加远高于对照侧。中缝核和黑质纹状体均损伤的大鼠,纹状体中多巴脱羧酶活性没有进一步降低,对多巴的生化或行为(旋转行为)反应也没有减弱。抑制脑毛细血管内皮细胞中含有的多巴脱羧酶,并没有消除损伤侧纹状体中多巴胺的生成,也没有消除给予多巴后的转圈行为。这些发现均提示,在没有多巴胺能神经元的情况下,纹状体中存在另一种细胞类型作为多巴脱羧的部位。

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The decarboxylation of DOPA in the parkinsonian brain: in vivo studies on an animal model.帕金森病大脑中多巴的脱羧作用:在动物模型上的体内研究
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