Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3,4-Dihydroxyphenylacetic Acid / metabolism
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5-Hydroxytryptophan / metabolism
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Biopterins / analogs & derivatives*
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Biopterins / deficiency*
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Biopterins / genetics
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Biopterins / pharmacology
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Dopamine / biosynthesis*
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Dopamine Antagonists / pharmacology
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Dystonic Disorders / drug therapy
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Dystonic Disorders / metabolism*
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Dystonic Disorders / physiopathology
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Homovanillic Acid / metabolism
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Humans
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Hydroxyindoleacetic Acid / metabolism
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Models, Biological
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Monoamine Oxidase Inhibitors / pharmacology
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Neuroblastoma
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Neurons / drug effects
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Neurons / metabolism*
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Serotonin / biosynthesis*
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Serotonin Antagonists / pharmacology
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Substantia Nigra / drug effects
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Substantia Nigra / metabolism*
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Substantia Nigra / physiopathology
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Tryptophan Hydroxylase / metabolism
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Tumor Cells, Cultured
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Tyrosine 3-Monooxygenase / metabolism*
Substances
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Dopamine Antagonists
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Monoamine Oxidase Inhibitors
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Serotonin Antagonists
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3,4-Dihydroxyphenylacetic Acid
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Biopterins
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Serotonin
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Hydroxyindoleacetic Acid
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5-Hydroxytryptophan
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Tyrosine 3-Monooxygenase
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Tryptophan Hydroxylase
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sapropterin
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Dopamine
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Homovanillic Acid