Ammonia at pathophysiologically relevant concentrations activates kynurenic acid synthesis in cultured astrocytes and neurons

Abstract

The synthesis of the NMDA receptor glycine site antagonist kynurenic acid (KYNA) from exogenously added kynurenine was measured in cultured cerebral cortical neurons, cortical astrocytes and an oligodendroglial cell line OLN-93, incubated for 2 h in the presence or absence of ammonium acetate (“ammonia”) at 0.1–10 mM concentration. In neurons ammonia stimulated KYNA synthesis to ∼160–170% of control at 0.1–1.0 mM, did not produce any effect at 2.5 and 5 mM, and inhibited the synthesis to ∼80% of control at 10 mM concentration. In astrocytes, a stimulation to ∼200% of control occurred in the whole ammonia concentration range. No effect of ammonia was noted in OLN-93 cells. Increased KYNA synthesis may represent a cytoprotective response of astrocytes and neurons against the NMDA receptor-mediated cytotoxic activity of ammonia.