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 Gi 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.