RESUMO
The stimulation of NMDA receptor increased [3H]GABA release from preloaded cultured retina cells. This effect appears to be mediated by NO production, since addition of L-NA reduces NMDA-evoked [3H]GABA release. Spermine/NO complex, an NO donor, mimics the effect produced by NMDA. The addition of zaprinast, a phosphodiesterase inhibitor, as well as 8-Br-cGMP enhances the NMDA-evoked [3H]GABA release. These results agree with the existence in chick retina cells of NO/cGMP pathways and support a role for NO in NMDA-evoked events. The activation of this receptor complex through maturative stages of the retina together with the NO-mediated increase in GABA release may account for NMDA differentiative effect in culturing retina cells.
Assuntos
N-Metilaspartato/farmacologia , Óxido Nítrico/farmacologia , Receptores de N-Metil-D-Aspartato/fisiologia , Retina/metabolismo , Ácido gama-Aminobutírico/metabolismo , 1-Metil-3-Isobutilxantina/farmacologia , Animais , Diferenciação Celular , Células Cultivadas , Embrião de Galinha , GMP Cíclico/análogos & derivados , GMP Cíclico/metabolismo , GMP Cíclico/farmacologia , Maleato de Dizocilpina/farmacologia , Isoquinolinas/farmacologia , Nitroarginina/farmacologia , Óxidos de Nitrogênio , Purinonas/farmacologia , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Retina/citologia , Retina/efeitos dos fármacos , Espermina/análogos & derivados , Espermina/farmacologia , TrítioRESUMO
Nitric oxide (NO) was investigated for its ability to induce amino acid release from immature chick retina. The production of endogenous NO by activation of NO synthase after stimulation of N-methyl-D-aspartate (NMDA) subtype of glutamate receptor caused a significant increase in basal release of gamma-aminobutyric acid (GABA) and glutamine, whereas a more modest increase in the glutamate release was also observed. The exposure of chick retina from 9-day-old embryos to NO-generating compounds, S-nitroso-N-acetylpe-nicillamine (SNAP) and sodium nitroprusside (SNP) produced a dose dependent increase in GABA, glutamine, and glutamate release. This effect was reduced by about 80% by haemoglobin. These results indicate that NO has a stimulatory effect on amino acid release from chick embryo immature retina. However, this effect does not appear to involve a cGMP-related mechanism because 8-bromo-cGMP, a stable analogue of cGMP, failed to affect spontaneous amino acid release and because zaprinast did not enhance NMDA-stimulated release. In conclusion, our present observations may account for a role of NMDA-mediated events in the biochemical maturation under depolarizing conditions.
Assuntos
Aminoácidos/metabolismo , Óxido Nítrico/farmacologia , Retina/embriologia , Retina/metabolismo , Animais , Embrião de Galinha , Relação Dose-Resposta a Droga , Desenvolvimento Embrionário e Fetal , Inibidores Enzimáticos/farmacologia , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Hemoglobinas/farmacologia , Nitroprussiato/farmacologia , Penicilamina/análogos & derivados , Penicilamina/farmacologia , Receptores de Glutamato/fisiologia , S-Nitroso-N-Acetilpenicilamina , Ácido gama-Aminobutírico/metabolismoRESUMO
High levels of nitric oxide synthase were found in the early stages of developing chick embryo retina. The enzyme activity sharply decreased up to 13-day-old chick embryo retina, when the level of the last embryonic day was reached. The results show that nitric oxide is synthesized in chick embryo retina prior to synaptogenesis. The incubation of chick embryo retinas in presence of NMDA increased the synthesis of nitric oxide, thus, the appearance of nitric oxide production before the synaptogenesis in the retina as well as in the brain may be considered as signal for the development and shaping of neuronal and non-neuronal cells.