Abstract:
:Catecholamine neurotransmitters--dopamine, noradrenaline (norepinephrine), adrenaline (epinephrine)--are synthesized in catecholaminergic neurons from tyrosine, via dopa, dopamine and noradrenaline, to adrenaline. Four enzymes are involved in the biosynthesis of adrenaline: (1) tyrosine 3-mono-oxygenase (tyrosine hydroxylase, TH); (2) aromatic L-amino acid decarboxylase (AADC, or DOPA decarboxylase, DDC); (3) dopamine beta-mono-oxygenase (dopamine beta-hydroxylase, DBH); and (4) noradrenaline N-methyltransferase (phenylethanolamine N-methyltransferase, PNMT). We cloned full-length complementary DNAs (cDNAs) and genomic DNAs of human catecholamine-synthesizing enzymes (TH, AADC, DBH, PNMT) and determined the nucleotide sequences and the deduced amino acid sequences. We discovered multiple messenger RNAs (mRNAs) of human TH, human DBH, and human PNMT. Four types (types 1, 2, 3, and 4) of human TH mRNAs are produced by alternative mRNA splicing mechanism from a single gene. We found the multiple forms of TH in two species of monkeys, but only a single mRNA corresponding to human TH type 1 in Sunkus murinus and rat, suggesting that the multiplicity of TH mRNA is primate-specific. Total TH mRNA, especially the most abundant type 2 and type 1 mRNAs in the human brain, were found to be reduced during the process of aging. The multiple forms of human TH may give additional regulation to the human enzyme, probably through altered phosphorylation and activation. We have succeeded in producing transgenic mice carrying multiple copies of the human TH gene in brain and adrenal medulla. The level of human TH mRNA in brain was about 50-fold higher than that of endogenous mouse TH mRNA. In situ hybridization demonstrated an enormous region-specific expression of the transgene in substantia nigra and ventral tegmental area. TH immunoreactivity in these regions, Western blot analysis, and TH activity measurements proved definitely increased TH in transgenic mice, though not comparable to the increment of the mRNA. However, catecholamine levels in transgenics were not significantly different from those in non-transgenics. The results suggest complex regulatory mechanisms for human TH gene expression and for the catecholamine levels in transgenic mice. Kohsaka and Uchida in collaboration with us applied genetically engineered (human TH cDNA-transfected) non-neuronal cells to brain tissue transplantation in parkinsonian rat models. We isolated and sequenced a full-length cDNA encoding human AADC.(ABSTRACT TRUNCATED AT 400 WORDS)
journal_name
Neurosci Resjournal_title
Neuroscience researchauthors
Nagatsu Tdoi
10.1016/0168-0102(91)90001-fsubject
Has Abstractpub_date
1991-10-01 00:00:00pages
315-45issue
2eissn
0168-0102issn
1872-8111pii
0168-0102(91)90001-Fjournal_volume
12pub_type
杂志文章,评审abstract::We studied the ascending and descending axonal trajectories of excitatory vestibular neurons related to the anterior semicircular canal, by means of local stimulation and spike-triggered signal averaging techniques in anesthetized cats. More than 200 vestibular neurons related to the ampullary nerve of the anterior se...
journal_title:Neuroscience research
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journal_title:Neuroscience research
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journal_title:Neuroscience research
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pub_type: 杂志文章
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journal_title:Neuroscience research
pub_type: 杂志文章
doi:10.1016/0168-0102(91)90042-w
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journal_title:Neuroscience research
pub_type: 杂志文章
doi:10.1016/s0168-0102(01)00306-6
更新日期:2002-01-01 00:00:00
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journal_title:Neuroscience research
pub_type: 杂志文章
doi:10.1016/s0168-0102(00)00148-6
更新日期:2000-09-01 00:00:00
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journal_title:Neuroscience research
pub_type: 杂志文章
doi:10.1016/s0168-0102(98)00100-x
更新日期:1998-12-01 00:00:00
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journal_title:Neuroscience research
pub_type: 杂志文章
doi:10.1016/j.neures.2016.03.001
更新日期:2016-09-01 00:00:00
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journal_title:Neuroscience research
pub_type: 杂志文章
doi:10.1016/0168-0102(89)90004-7
更新日期:1989-06-01 00:00:00
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journal_title:Neuroscience research
pub_type: 杂志文章
doi:10.1016/0168-0102(91)90101-4
更新日期:1991-10-01 00:00:00
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journal_title:Neuroscience research
pub_type: 杂志文章,评审
doi:10.1016/j.neures.2013.10.001
更新日期:2014-01-01 00:00:00
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journal_title:Neuroscience research
pub_type: 杂志文章
doi:10.1016/s0168-0102(03)00188-3
更新日期:2003-10-01 00:00:00
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journal_title:Neuroscience research
pub_type: 杂志文章
doi:10.1016/0168-0102(88)90003-x
更新日期:1988-10-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.neures.2019.02.001
更新日期:2020-01-01 00:00:00
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journal_title:Neuroscience research
pub_type: 杂志文章
doi:10.1016/j.neures.2008.01.001
更新日期:2008-04-01 00:00:00
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journal_title:Neuroscience research
pub_type: 杂志文章
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journal_title:Neuroscience research
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更新日期:1996-06-01 00:00:00
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doi:10.1016/s0168-0102(00)00195-4
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journal_title:Neuroscience research
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更新日期:2002-08-01 00:00:00
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journal_title:Neuroscience research
pub_type: 杂志文章
doi:10.1016/j.neures.2015.11.007
更新日期:2016-05-01 00:00:00
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journal_title:Neuroscience research
pub_type: 杂志文章
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更新日期:2020-07-01 00:00:00
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journal_title:Neuroscience research
pub_type: 杂志文章,评审
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journal_title:Neuroscience research
pub_type: 杂志文章
doi:10.1016/j.neures.2009.04.015
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journal_title:Neuroscience research
pub_type: 杂志文章
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更新日期:1996-08-01 00:00:00
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journal_title:Neuroscience research
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doi:10.1016/j.neures.2012.08.005
更新日期:2012-10-01 00:00:00
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journal_title:Neuroscience research
pub_type: 杂志文章
doi:10.1016/j.neures.2004.07.006
更新日期:2004-11-01 00:00:00
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journal_title:Neuroscience research
pub_type: 杂志文章
doi:10.1016/j.neures.2012.01.008
更新日期:2012-04-01 00:00:00
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journal_title:Neuroscience research
pub_type: 杂志文章
doi:10.1016/j.neures.2005.03.006
更新日期:2005-06-01 00:00:00