Dopamine promotes NMDA receptor hypofunction in the retina through D-1 receptor-mediated Csk activation, Src inhibition and decrease of GluN2B phosphorylation

• Tipo: Artigo em Revista Científica Internacional
• Data: 2017

Autores

Socodato, R (Autor) Outra; Santiago, FN (Autor) Outra; Portugal, CC (Autor) Outra; Domith, I (Autor) Outra; Encarnacao, TG (Autor) Outra; Loiola, EC (Autor) Outra; Ventura, ALM (Autor) Outra; Cossenza, M (Autor) Outra; Relvas, JB (Autor) ICBAS; Castro, NG (Autor) Outra; Paes de Carvalho, R (Autor) Outra

Revista

Título: Scientific Reports

Vol. 7

ISSN: 2045-2322

Editora: Springer Nature

Indexação

ISI Web of Knowledge - 9 Citações

Scopus - 15 Citações

Outras Informações

ID Authenticus: P-00M-CK9

DOI: 10.1038/srep40912

Abstract (EN): Dopamine and glutamate are critical neurotransmitters involved in light-induced synaptic activity in the retina. In brain neurons, dopamine D-1 receptors (D(1)Rs) and the cytosolic protein tyrosine kinase Src can, independently, modulate the behavior of NMDA-type glutamate receptors (NMDARs). Here we studied the interplay between D1Rs, Src and NMDARs in retinal neurons. We reveal that dopamine-mediated D1R stimulation provoked NMDAR hypofunction in retinal neurons by attenuating NMDA-gated currents, by preventing NMDA-elicited calcium mobilization and by decreasing the phosphorylation of NMDAR subunit GluN2B. This dopamine effect was dependent on upregulation of the canonical D1R/adenylylcyclase/cAMP/PKA pathway, of PKA-induced activation of C-terminal Src kinase (Csk) and of Src inhibition. Accordingly, knocking down Csk or overexpressing a Csk phosphoresistant Src mutant abrogated the dopamine-induced NMDAR hypofunction. Overall, the interplay between dopamine and NMDAR hypofunction, through the D1R/Csk/Src/GluN2B pathway, might impact on light-regulated synaptic activity in retinal neurons.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 14