6R-Tetrahydrobiopterin induces dopamine synthesis in a human neuroblastoma cell line, LA-N-1. A cellular model of DOPA-responsive dystonia.
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.
Zuddas
Alessandro
A
Child NeuroPsychiatry, Department of Neuroscience, University of Cagliari, Via Ospedale 119, 09124 Cagliari, Italy. azuddas@unica.it
Mancosu
Cristina
C
Lilliu
Vanessa
V
Sorrentino
Giuseppe
G
di Porzio
Umberto
U
Cianchetti
Carlo
C
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D006916:5-Hydroxytryptophan / Q000378:metabolism; D001708:Biopterins / Q000031:analogs & derivatives* / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology; D004298:Dopamine / Q000096:biosynthesis*; D018492:Dopamine Antagonists / Q000494:pharmacology; D020821:Dystonic Disorders / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008954:Models, Biological; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000096:biosynthesis*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D018492:Dopamine Antagonists; D008996:Monoamine Oxidase Inhibitors; D012702:Serotonin Antagonists; D015102:3,4-Dihydroxyphenylacetic Acid; D001708:Biopterins; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D006916:5-Hydroxytryptophan; D014446:Tyrosine 3-Monooxygenase; D014365:Tryptophan Hydroxylase; C003402:sapropterin; D004298:Dopamine; D006719:Homovanillic Acid