Abstract：
:Dopamine (DA) is a classical neurotransmitter modulating various brain functions by acting on its specific receptors. In addition, DA is a reactive molecule that has been implicated in neurodegeneration, especially in Parkinson's disease. Here we show that DA inhibited cell growth of dopamine transporter transfected cells by intracellularly blocking cell cycle progression. To pinpoint the site of this effect, we measured DNA distribution and 5-bromo-2'-deoxyuridine (BrdU) incorporation, as well as the levels of the key cell cycle proteins. DA increased number of cells with a G1 DNA content, decreased BrdU incorporation and simultaneously increased cyclin A but had no effect on cyclin D2, D3, E, nor on cdk4 and p21. These results narrowed down the DA effect to the beginning of S phase, suggesting inhibition of the ribonucleotide reductase, an enzyme essential for DNA synthesis. Indeed, measurement of enzyme activity in situ revealed that DA, within 1h of addition to cells labelled with [3H]cytidine, strongly reduced the cell content of [3H]2'-deoxycytidine 5'-triphophate. The time course of this DA effect preceded the cell cycle progression. This novel molecular mechanism of intracellular DA action independent of plasmamembrane receptors may be involved in processes controlling the development and survival of brain dopaminergic neurons.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Woldman I,Reither H,Kattinger A,Hornykiewicz O,Pifl Cdoi
10.1016/j.neuropharm.2004.11.013subject
Has Abstractpub_date
2005-03-01 00:00:00pages
525-37issue
4eissn
0028-3908issn
1873-7064pii
S0028-3908(04)00392-2journal_volume
48pub_type
杂志文章abstract：:2-[p-(2-carboxyethyl)-phenylethylamino]-5'-N-ethylcarboxamidoadeno sine (CGS 21680) is considered a selective ligand for adenosine A2A receptors, which are known to be enriched in striatum and olfactory tubercle. We have investigated the characteristics of [3H]CGS 21680 binding in several brain regions using quantitat...
journal_title：Neuropharmacology
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pub_type： 杂志文章
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更新日期：2006-02-01 00:00:00
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pub_type： 杂志文章
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(87)90018-9
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pub_type： 杂志文章
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更新日期：2019-10-01 00:00:00
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更新日期：2013-03-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
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更新日期：2006-09-01 00:00:00
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pub_type： 杂志文章
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更新日期：1987-10-01 00:00:00
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journal_title：Neuropharmacology
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