Induction of astrocyte glutamine synthetase activity by the lathyrus toxin β-N-oxalyl-L-α,β-diaminopropionic acid (β-L-ODAP)

✍ Scribed by Stephan Miller; Peter B. Nunn; Richard J. Bridges

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 1020 KB
• Volume: 7
• Category: Article
• ISSN: 0894-1491
• DOI: 10.1002/glia.440070408

✦ Synopsis

p-N-Oxalyl-L-a$-diaminopropionic acid (P-L-ODAP) is thought to be the causative agent in lathyrism due to its neuroexcitatory and neurotoxic properties. We have recently reported that P-L-ODAF' is also gliotoxic at high concentrations (Bridges et al.: Brain Res 561:262, 1991). Evidence is now presented that low, subgliotoxic concentrations of 0-L-ODAP may alter the ability of astrocytes to regulate glutamate concentrations in the CNS by increasing astrocyte glutamine synthetase activity. When astrocytes cultured from rat cortex were exposed to 100 pM P-L-ODAP for 24 h, the resulting glutamine synthetase activity was 155% of control levels. This effect was enantiomerand isomer-specific, dose-dependent, and required protein translation as the induction was blocked with cycloheximide. The effect of P-L-ODAP on glutamine synthetase was not mimicked by a-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) or kainate, suggesting that the induction was not transduced solely through activation of cell surface non-N-methyl-D-aspartate (NMDA) glutamate receptors. An intracellular site of action of p-L-OD@ is proposed because its effect on glutamine synthetase activity could be blocked by the amino acid uptake blocker dihydrokainate.