Zuddas Alessandro, Mancosu Cristina, Lilliu Vanessa, Sorrentino Giuseppe, di Porzio Umberto, Cianchetti Carlo
Child NeuroPsychiatry, Department of Neuroscience, University of Cagliari, Via Ospedale 119, 09124 Cagliari, Italy.
Brain Res. 2002 Jul 12;943(2):257-62. doi: 10.1016/s0006-8993(02)02694-x.
Dopa-responsive dystonia (DRD) is an extrapyramidal disorder caused by deficit of 5,6,7,8-tetrahydrobiopterin (BH4), cofactor for tyrosine hydroxylase (TH). In these patients the nigrostriatal dopaminergic neurons normally express TH and the cellular machinery for the dopamine uptake. LA-N-1 is a human neuroblastoma cell line expressing tyrosine hydroxylase. Here we show that LA-N-1 cells are able to take up exogenous dopamine (DA) by an high-affinity mechanism; significant amounts of serotonin and its metabolite 5HIAA, but neither DA nor its metabolites, DOPAC and HVA, could be measured in the cell culture homogenate. 5,6,7,8-Tetrahydrobiopterin, cofactor for both tyrosine and tryptophan hydroxylases, is able to activate dopamine synthesis and also decreases the content of 5HIAA by 50%, indicating that LA-N-1 might be a useful model for studying dopamine-serotonin interaction in cultured cells and the neuronal mechanism of DRD.
多巴反应性肌张力障碍（DRD）是一种锥体外系疾病，由酪氨酸羟化酶（TH）的辅因子5,6,7,8-四氢生物蝶呤（BH4）缺乏引起。在这些患者中，黑质纹状体多巴胺能神经元通常表达TH以及多巴胺摄取的细胞机制。LA-N-1是一种表达酪氨酸羟化酶的人神经母细胞瘤细胞系。在这里，我们表明LA-N-1细胞能够通过高亲和力机制摄取外源性多巴胺（DA）；在细胞培养匀浆中无法检测到大量的血清素及其代谢物5HIAA，但未检测到DA及其代谢物DOPAC和HVA。酪氨酸和色氨酸羟化酶的辅因子5,6,7,8-四氢生物蝶呤能够激活多巴胺合成，还能使5HIAA的含量降低50%，这表明LA-N-1可能是研究培养细胞中多巴胺-血清素相互作用以及DRD神经元机制的有用模型。
