Glutamate receptors coupled to nitric oxide synthesis in embryonic retina

Existing evidence suggests a role for nitric oxide (NO) in the establishment of stable synaptic connections during the embryonic development of the central nervous system. In the visual system, the participation of NO in programmed cell death, the natural elimination of photoreceptors and the modulation of photoreceptor ion channels has been documented. In the present work, the effect of ionotropic and metabotropic glutamate receptor (GluR) agonists on NO synthesis in the chick retina was studied at embryonic day (ED) 14, in which active synaptogenesis takes place, and compared with that in the mature tissue. We showed that at ED 14, N-methyl-D-aspartate, kainate and trans-(1S,3R)-1-amino-1,3-cyclopentanedicarboxylate stimulate NO formation at low concentrations, whereas high concentrations of the drugs inhibit NO synthesis. The results suggest the participation of GluR-induced NO synthesis in differentiation and synaptogenesis, and demonstrate a negative feedback of GluR stimulation on NO synthesis by nonphysiological glutamate concentrations, which could be relevant to neuronal protection from glutamate-induced toxicity in the retina during a critical period of embryonic development.