INVESTIGADORES
DORFMAN Damian
artículos
Título:
Effect of Angeli's salt on the glutamate/glutamine cycle activity and on glutamate excitotoxicity in the hamster retina.
Autor/es:
KNOTT ME; DORFMAN D; CHIANELLI MS; SÁENZ DA
Revista:
NEUROCHEMISTRY INTERNATIONAL
Editorial:
PERGAMON-ELSEVIER SCIENCE LTD
Referencias:
Lugar: Amsterdam; Año: 2012 vol. 61 p. 7 - 15
ISSN:
0197-0186
Resumen:
Glutamate
is the main excitatory neurotransmitter in the retina, but it is toxic when
present in excessive amounts. It is well known that NO is involved in glutamate
excitotoxicity, but information regarding the possibility that NO-related
species could reciprocally affect glutamate synaptic levels was not previously
provided. The dependence of glutamatergic neurons upon glia via the
glutamate/glutamine cycle to provide the precursor for neurotransmitter
glutamate is well established. The aim of the present work was to comparatively
analyze the effect of nitroxyl and NO on the retinal glutamate/glutamine cycle
in vitro activity. For this purpose, Angeli´s salt (AS) and diethylamine
NONOate (DEA/NO) were used as nitroxyl and NO donor, respectively. AS and
DEA/NO significantly decreased retinal l-glutamate uptake and glutamine
synthetase activity, but only AS decreased l-glutamine influx. Dithiothreitol
prevented all the effects of AS and DEA/NO. The intravitreal injection of
DEA/NO (but not AS) or a supraphysiological concentration of glutamate induced
retinal histological alterations. Although AS could increase glutamate synaptic
concentration in vitro, the histological alterations induced by glutamate were
abrogated by AS. These results suggest that nitroxyl could regulate the hamster
retinal glutamatergic pathway by acting through differential mechanisms at pre-
and postsynaptic level.