Role of glutamate receptors and glutamate transporters in the regulation of the glutamate-glutamine cycle in the awake rat

In the present study we investigate the effects of a specific glutamate reu ptake blocker, L-trans-pyrrolidine-3,4-dicarboxylic acid (PDC), on extracel lular concentrations of glutamine and glutamate in the striatum of the free ly moving rat. Intracerebral infusions of PDC (1, 2 and 4 mM) produced a do se-related increase in extracellular concentrations of glutamate and a dose -related decrease in extracellular concentrations of glutamine. These incre ases in extracellular glutamate and decreases in extracellular glutamine we re significantly correlated. To investigate the involvement of ionotropic g lutamate receptors in the decreases of extracellular glutamine produced by PDC, N-methyl-D-aspartate (NMDA) receptor antagonist and alpha-amino-3-hydr oxy-5-methylisoxazole-4-propionate (AMPA)/kainate receptor antagonist were used. Perfusion of the NMDA receptor antagonist blocked the decrease of ext racellular glutamine but had no effect on the increase of extracellular glu tamate, both produced by PDC. Perfusion of the AMPA/kainate receptor antago nist attenuated the increase of extracellular glutamate and not only blocke d the decrease of extracellular glutamine but also produced a significant i ncrease of extracellular glutamine. The results reported in this study sugg est that both NMDA and AMPA/kainate glutamatergic receptors are involved in the regulation of extracellular glutamine.