Attenuation of levodopa-induced toxicity in mesencephalic cultures by pramipexole
Attenuation of levodopa-induced toxicity in mesencephalic cultures by pramipexole
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DOI：
10.1007/bf01273182
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发表时间：
1997-01-01
影响因子：
3.3
通讯作者：
Ling, ZD
中科院分区：
文献类型：
--
作者：
Carvey, PM;Pieri, S;Ling, ZD
评估了直接作用的多巴胺 (DA) 激动剂普拉克索（2 氨基-3,4,5,6,7-四氢-6-丙基-氨基-苯并噻唑-二盐酸盐）在中脑培养物中减弱左旋多巴诱导的酪氨酸羟化酶免疫反应性（THir，多巴胺神经元标记物）细胞丧失的能力。普拉克索以剂量依赖性和可饱和的方式减少左旋多巴诱导的 THir 细胞损失 (ED50 = 500 pM)，其无活性立体异构体在这方面的效力明显较差，培高利特和溴隐亭的细胞保护作用可以忽略不计。来自与普拉克索一起孵育 6 天的中脑培养物的培养基增加了新鲜收获的受体培养物中的 THir 细胞计数。这种效应的大小与供体培养物中普拉克索的量成正比，并且培养基的热灭活消除了生长促进效应。这组探索性实验的结果表明，普拉克索可能对组织培养中的多巴胺神经元具有细胞保护作用。普拉克索对 DA 受体的亲和力、其抗氧化作用或其增强中脑营养活性的能力可能是造成这种效果的原因。
The direct-acting dopamine (DA) agonist pramipexole (2 amino-3,4,5,6,7-tetrahydro-6-propyl-amino-benzthiazole-dihydrochloride) was evaluated for its ability to attenuate levodopa-induced loss of tyrosine hydroxylase immunoreactive (THir, a marker for dopamine neurons) cells in mesencephalic cultures. Pramipexole reduced levodopa-induced THir cell loss in a dose-dependent and saturable fashion (ED50 = 500 pM), its inactive stereoisomer was significantly less potent in this regard and pergolide and bromocriptine had negligible cytoprotective effects. Culture media from mesencephalic cultures incubated with pramipexole for 6 days increased THir cell counts in freshly harvested recipient cultures. The magnitude of this effect was directly proportional to the amount of pramipexole in the donor cultures and heat-inactivation of the media abolished the growth promoting effect. The results from this exploratory set of experiments suggest that pramipexole may be cytoprotective to dopamine neurons in tissue culture. Pramipexole's affinity for DA receptors, its antioxidant action or its ability to enhance mesencephalic trophic activity could be responsible for this effect.