Premium
Glutamate and nitric oxide modulate ERK and CREB phosphorylation in the avian retina: evidence for direct signaling from neurons to Müller glial cells
Author(s) -
Socodato Renato Esteves da Silva,
Magalhães Cristiane Rosa,
PaesdeCarvalho Roberto
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05778.x
Subject(s) - creb , glutamate receptor , microbiology and biotechnology , nmda receptor , soluble guanylyl cyclase , protein kinase a , biology , phosphorylation , signal transduction , chemistry , biochemistry , receptor , transcription factor , guanylate cyclase , gene
Glutamate signaling in the mature retinal tissue is very important for accurate sensory decoding by retinal neurons and orchestrates the fine‐tuned output from the retina to higher‐order centers at the cerebral cortex. In this study, we show that glutamate induces a rapid extracellular‐regulated kinase and cAMP‐responsive element binding protein (CREB) phosphorylation in cultured developing retinal neurons. This process is reliant on α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate receptors and nitric oxide (NO) signaling and independent of NMDA receptors activation, as it is blocked by α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate/kainate antagonists as well as inhibiting NO synthase with NG‐nitro‐ l ‐arginine methyl ester but not by the NMDA channel blocker dizocilpine maleate. The effect of NO on extracellular‐regulated kinase and CREB is mediated by the classical NO/soluble guanylyl cyclase/protein kinase G pathways as it is inhibited by the soluble guanylyl cyclase blocker 1H‐[1,2,4]oxadiazole[4,3‐a]quinoxalin‐1‐one and the protein kinase G inhibitor KT5823, respectively. Immunocytochemical data suggest that increased CREB phosphorylation in response to glutamate occurs in glial cell nuclei. We also have supporting evidence suggesting that neuronally produced NO directly reaches the glial cells and stimulates CREB phosphorylation. Hence, the results indicate the importance of neuronal–glial communication and glutamate/NO/CREB linkage during retinal development.