Dopamine Promotes Ascorbate Release from Retinal Neurons: Role of D1 Receptors and the Exchange Protein Directly Activated by cAMP type 2 (EPAC2)

Molecular Neurobiology
Thaísa Godinho da EncarnaçãoRoberto Paes-de-Carvalho

Abstract

Ascorbate, the reduced form of vitamin C, is highly concentrated in the central nervous system (CNS), including the retina, where it plays important physiological functions. In the CNS, the plasma membrane transporter sodium vitamin C co-transporter 2 (SVCT2) is responsible for ascorbate transport in neurons. The neurotransmitter dopamine (DA), acting through D1- and D2-like receptor subfamilies and classically coupled to adenylyl cyclase, is known to modulate synaptic transmission in the retina. Here, we reveal that DA controls the release of ascorbate from retinal neurons. Using primary retinal cultures, we show that this DA effect is dose-dependent, occurring by the reversal of the SVCT2, and could be elicited by brief and repetitive pulses of DA. The DA effect in inducing ascorbate release occurs by the activation of D1R and is independent of PKA. Moreover, the exchange protein directly activated by cAMP type 2 (EPAC2) is present in retinal neurons and its specific knockdown using shRNAs abrogates the D1R-induced ascorbate release. Confirming the physiological relevance of this pathway, activation of D1R or EPAC2 also triggered ascorbate release ex vivo in acute preparations of the intact retina. Overall, DA plays pivotal r...Continue Reading

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Methods Mentioned

BETA
nucleotide exchange
deamination
confocal microscopy
pull-down
protein assay
electrophoresis

Software Mentioned

LAS AF
Graph Pad Prism
Image J

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