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SIGMA1 Receptor Modulation of Dopamine Transporter: Molecular Analysis   Nicola Fazio

SIGMA1 Receptor Modulation of Dopamine Transporter: Molecular Analysis

240 страниц. 2012 год.
LAP Lambert Academic Publishing
Sigma (?) receptors are well established as an indipendent receptor family with its characteristic binding profile and distribution in the central nervous system. Activation of ?1 receptors alters several neurotransmitter systems, in particular the dopamine (DA) neurotrasmission; however the exact role of ?1 receptor in dopaminergic homeostasis remains unclear. The DA transporter (DAT) is the primary mechanism by wich dopaminergic neurons terminate the signal, thus regulating the temporal aspects of dopaminergic synaptic transmission. This study shows for the first time that, in cell models, ?1 receptors directly modulate the DAT activity. Facilitation of DA uptake induced by (+)-pentazocine, a powerful ?1 agonist, is reflected on the increased cell susceptibility to DA toxicity; these effects are prevented by ?1 selective antagonists. Since numerous compounds, including several drugs of abuse, activate ?1 receptors, thus eliciting a severe dopaminergic neurons damage, the reported...
 
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