Dopamine promotes NMDA receptor hypofunction in the retina through D₁ receptor-mediated Csk activation, Src inhibition and decrease of GluN2B phosphorylation.

ABSTRACT: Dopamine and glutamate are critical neurotransmitters involved in light-induced synaptic activity in the retina. In brain neurons, dopamine D₁ receptors (D₁Rs) 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/adenylyl cyclase/cAMP/PKA pathway, of PKA-induced activatio

SUBMITTER: Socodato R 

PROVIDER: S-EPMC5241882 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature