Source:http://linkedlifedata.com/resource/pubmed/id/20976142
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
10
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pubmed:dateCreated |
2010-10-26
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pubmed:abstractText |
Dopamine (3-hydroxytyramine) is a well-known catecholamine neurotransmitter involved in multiple physiological functions including movement control. Here we report that the major extracellular metabolite of dopamine, 3-methoxytyramine (3-MT), can induce behavioral effects in a dopamine-independent manner and these effects are partially mediated by the trace amine associated receptor 1 (TAAR1). Unbiased in vivo screening of putative trace amine receptor ligands for potential effects on the movement control revealed that 3-MT infused in the brain is able to induce a complex set of abnormal involuntary movements in mice acutely depleted of dopamine. In normal mice, the central administration of 3-MT caused a temporary mild hyperactivity with a concomitant set of abnormal movements. Furthermore, 3-MT induced significant ERK and CREB phosphorylation in the mouse striatum, signaling events generally related to PKA-mediated cAMP accumulation. In mice lacking TAAR1, both behavioral and signaling effects of 3-MT were partially attenuated, consistent with the ability of 3-MT to activate TAAR1 receptors and cause cAMP accumulation as well as ERK and CREB phosphorylation in cellular assays. Thus, 3-MT is not just an inactive metabolite of DA, but a novel neuromodulator that in certain situations may be involved in movement control. Further characterization of the physiological functions mediated by 3-MT may advance understanding of the pathophysiology and pharmacology of brain disorders involving abnormal dopaminergic transmission, such as Parkinson's disease, dyskinesia and schizophrenia.
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pubmed:grant | |
pubmed:commentsCorrections | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:issn |
1932-6203
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
5
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
e13452
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pubmed:dateRevised |
2011-3-8
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pubmed:meshHeading |
pubmed-meshheading:20976142-Animals,
pubmed-meshheading:20976142-Behavior, Animal,
pubmed-meshheading:20976142-Blotting, Western,
pubmed-meshheading:20976142-Corpus Striatum,
pubmed-meshheading:20976142-Cyclic AMP Response Element-Binding Protein,
pubmed-meshheading:20976142-Dopamine,
pubmed-meshheading:20976142-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:20976142-Humans,
pubmed-meshheading:20976142-Mice,
pubmed-meshheading:20976142-Mice, Inbred C57BL,
pubmed-meshheading:20976142-Mice, Knockout,
pubmed-meshheading:20976142-Phosphorylation,
pubmed-meshheading:20976142-Signal Transduction
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pubmed:year |
2010
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pubmed:articleTitle |
The dopamine metabolite 3-methoxytyramine is a neuromodulator.
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pubmed:affiliation |
Department of Neuroscience and Brain Technologies, Italian Institute of Technology, Genova, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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