Kynurenic acid actions in brain and periphery

Kynurenic acid (KYNA) is commonly considered a non-competitive NMDA receptor antagonist. It has been recently shown that KYNA also antagonizes the alpha 7 nicotine receptors and reduces glutamate and dopamine release in the rat striatum. Finally, it has been demonstrated that KYNA interacts with GPR35, an orphan receptor negatively coupled to G_i proteins.

We noticed that in a macrophage cell line (RAW 264.7) KYNA reduces the LPS-induced release of pro-inflammatory cytokines. In mice treated with lethal doses of LPS, a septic shock model, KYNA administration (200 mg/kg i.p.x 3 times) significantly reduced the mortality rate. Thus KYNA has receptors both in the nervous and peripheral tissues where it may play an interesting regulatory role in cell activation and survival.