1-Aminocyclopentane-trans-1,3-Dicarboxylic Acid Induces Glutamine Synthetase Activity in Cultured Astrocytes

: In this study we have investigated the effect of excitatory amino acids on the activity of glutamine synthetase, a glial-specific enzyme that plays a key role in the regulation of glutamate concentration in the CNS. We found that of L-glutamate, N-methyl-D-aspartate, α-amino-3-hydroxy-5-methylisoxazole-4-propionate, kainate, and 1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD), only the metabotropic glutamate receptor agonist trans-ACPD had an effect on glutamine synthetase specific activity in cultures of rat type I cortical astrocytes. Exposure of astrocytes to 1.0 mMtrans-ACPD for 24 h resulted in an increase in glutamine synthetase activity to 149 ± 11% of that in control cultures. This effect was concentration dependent, stereoselective, and blocked by cycloheximide. In addition, the increase in glutamine synthetase activity occurred at lower concentrations of trans-ACPD that did not produce morphological alterations or lysis of the astrocytes as measured by the lactate dehydrogenase content. These findings are consistent with the hypothesis that activation of the metabotropic excitatory amino acid receptor in astrocytes is coupled to the regulation of an enzyme essential to the metabolism and recycling of the excitatory transmitter L-glutamate.