The dopamine metabolite 3-methoxytyramine is a neuromodulator.
Data(s) |
18/10/2010
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Identificador |
http://www.ncbi.nlm.nih.gov/pubmed/20976142 PLoS One, 2010, 5 (10), pp. e13452 - ? http://hdl.handle.net/10161/4579 1932-6203 |
Idioma(s) |
ENG en_US |
Relação |
PLoS One 10.1371/journal.pone.0013452 Plos One |
Tipo |
Journal Article |
Cobertura |
United States |
Resumo |
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. |
Formato |
e13452 - ? |
Palavras-Chave | #Animals #Behavior, Animal #Blotting, Western #Corpus Striatum #Cyclic AMP Response Element-Binding Protein #Dopamine #Extracellular Signal-Regulated MAP Kinases #Humans #Mice #Mice, Inbred C57BL #Mice, Knockout #Phosphorylation #Signal Transduction |