Human Nigrostriatal Dopamine Neurons Express Low Levels of GTP Cyclohydrolase I mRNA
GTP cyclohydrolase I (GTPCH; EC 184.108.40.206) is the first and rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin (BH4) (1). BH4 is the required cofactor for the family of aromatic amino acid monoxygenases that includes tyrosine hydroxylase, tryptophan hydroxylase, and phenylalanine hydroxylase (2). BH4 is also essential for activity of the nitric oxide synthases (3,4). Monoamine and nitric oxide synthesis are therefore influenced by BH4 availability. GTPCH expression in human (5), rat (6, 7, 8, 9) and mouse (10,11) brain has been localized at the cellular level to monoamine-secreting neurons. GTPCH mRNA abundance in rat and mouse brain (7, 11) and GTPCH protein content in rat brain (9) are heterogeneous across different population of monoaminergic neurons, with low levels found within nigrostriatal dopamine neurons and high levels within the serotonin neurons of the dorsal raphe.
KeywordsLocus Coeruleus Dorsal Raphe Phenylalanine Hydroxylase Serotonin Neuron Nigrostriatal Dopaminergic Neuron
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