Glutamate and nitric oxide modulate ERK and CREB phosphorylation in the avian retina: evidence for direct signaling from neurons to Müller glial cells.
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 alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors and nitric oxide (NO) signaling and independent of NMDA receptors activation, as it is blocked by alpha-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.
Socodato
Renato Esteves da Silva
RE
Department of Neurobiology and Program of Neurosciences, Institute of Biology, Fluminense Federal University, Niterói, RJ, Brazil.
Magalhães
Cristiane Rosa
CR
Paes-de-Carvalho
Roberto
R
D000818:Animals; D050882:CREB-Binding Protein / Q000378:metabolism*; D002450:Cell Communication / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D018698:Glutamic Acid / Q000494:pharmacology*; D066298:In Vitro Techniques; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D012160:Retina / Q000166:cytology* / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D013778:Tetrazolium Salts; D013844:Thiazoles; D013997:Time Factors
D004791:Enzyme Inhibitors; D018683:Excitatory Amino Acid Agents; D020030:Nitric Oxide Donors; C110881:S-nitro-N-acetylpenicillamine; D013778:Tetrazolium Salts; D013844:Thiazoles; D009569:Nitric Oxide; D018698:Glutamic Acid; D050882:CREB-Binding Protein; D048049:Extracellular Signal-Regulated MAP Kinases; C022616:thiazolyl blue; D010396:Penicillamine