Lourdes A. Vega Rasgado, Guillermo Ceballos Reyes and Fernando Vega DÃÆÃÂaz
Glutamate (GLU), the major excitatory neurotransmit ter in central nervous system, participates in several pathologies such as epilepsy and also in in tracellular signaling functions via its metabolism through glutamate dehydrogenase (GDH, E.C. 220.127.116.11. ). Considering that GDH is a key enzyme for GLU biosynthesis and modulation and, an indirect γ -aminobutyric acid (GABA) source, here we studied t he effect of some chemoconvulsants such as pentilenete trazole (PTZ), thiosemicarbazide (TS) and bicuculline (BIC) on mouse brain GDH activity in vitro and ex vivo , to explore the possible participation of GDH in seizures mechanism. Convulsants influence in oxygen consumption in vitro and ex vivo was also investigated, since glutamate is a glucogenic aminoacid and anoxia is a primary cause of convulsions. In vitro , all convulsants decreased GLU oxidative deaminati on and oxygen consumption when α Ketoglutarate ( α K) reductive amination was catalyzed. Ex vivo , all convulsants increased α K reductive amination and oxygen consumption with thi s substrate. Results suggest that, during seizures, GDH increase GLU levels which induced chan ges in oxygen consumption. Changes on GDH activity may result from changes on GABA levels thr ough T-GABA activity modulation and/or in energy requirements caused by convulsions, making GDH an i mportant regulation point of GLU and indirectly of GABA levels, thus of neuronal excitability.
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