The Janus-face kynurenic acid

Abstract

Kynurenic acid is an endogenous product of the tryptophan metabolism. Studies on the mechanism of its action have revealed that kynurenic acid at high concentrations is a competitive antagonist of the N-methyl-D-aspartate receptor and acts as a neuroprotectant in different neurological disorders. This in vitro investigation was designed to show that kynurenic acid acts differently at low concentrations. In vitro electrophysiological examinations on the young rat hippocampus confirmed the well-known finding that kynurenic acid in micromolar concentrations exerts an inhibitory effect. However, in nanomolar concentrations, kynurenic acid does not give rise to inhibition, but in fact facilitates the field excitatory postsynaptic potentials. The results available so far are compatible with the idea that kynurenic acid in the concentration range between a few hundred nanomolar and micromolar displays different effects. Its probable action on different receptors, inducing the different mechanisms, is discussed. The findings strongly suggest the neuromodulatory role of kynurenic acid under both physiological and pathological circumstances.

Alzheimer’s Disease: Recent Concepts on the Relation of Mitochondrial Disturbances, Excitotoxicity, Neuroinflammation, and Kynurenines

“…However, the basal extracellular concentration of KYNA in rats (15-23 nM) is far below the required level, i.e., ~10-20 μM concentrations, to directly interfere with NMDAR functions under physiological concentrations [208,271,272]. Of note, KYNA has been demonstrated to have a dose-dependent dual action on AMPA receptors, as in low (nM to µM) concentrations, KYNA is capable of facilitating AMPA receptor responses with a potential positive effect on LTP, whereas in higher concentrations it has inhibitory effects, which may interfere with LTP formation and may be associated with cognitive dysfunctions [273,274]. Though the most widely recognized and generally hypothesized neuroprotective [277,[281][282][283][284].…”

Effect of dietary administration of kynurenic acid on the activity of splenocytes of the rainbow trout (Oncorhynchus mykiss)

“…A strong expression of these receptors has been observed on monocytes, T cells, neutrophils and dendritic cells; a weaker expression was noticed on B cells, eosinophils, basophils and NKT cells. The immunotropic properties of KYNA described so far, and originating from its reaction with GPR35 receptors, are predominantly associated with the anti-inflammatory action [2][3][4][5]. Apart from immune cells, GPR35 receptors are also present on the surface of enterocytes in intestinal crypts, which may imply some involvement of KYNA in the local immunologic response in the digestive tract and in the functions performed by enterocytes.…”

Systemic administration of l -kynurenine sulfate induces cerebral hypoperfusion transients in adult C57Bl/6 mice

“…As such, KYNA was shown to facilitate excitatory postsynaptic potentials at low concentration, but it exerts inhibitory effect at higher-concentration, through dual actions on α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (Prescott et al, 2006;Rózsa et al, 2008). Therefore, it is reasonable to propose that the effect of L-KYNs on CBF is also dose dependent.…”