The Dopamine Metabolite 3-Methoxytyramine Is a NeuromodulatorReportar como inadecuado




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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.



Autor: Tatyana D. Sotnikova, Jean-Martin Beaulieu, Stefano Espinoza, Bernard Masri, Xiaodong Zhang, Ali Salahpour, Larry S. Barak, Marc

Fuente: http://plos.srce.hr/



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