Impairment of brain kynurenic acid production by glutamate metabotropic receptor agonists

Abstract

The role of glutamatergic mechanisms in kynurenic acid (KYNA) production was evaluated in vitro. The selective ionotropic agonists NMDA, kainate and AMPA did not affect KYNA synthesis. Agonists of metabotropic (mGLU) and ionotropic receptors: quisqualate, L-glutamate and L-aspartate as well as agonists of mGLU receptors: (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (t-ACPD) and L-(+)-2-amino-4-phosphonobutyric acid (L-AP4) diminished KYNA production with different potency. None of the studied mGLU antagonists such as (S)-4-carboxyphenylglycine, alpha-ethylglutamic acid or (RS)-alpha-methylserine-O-phosphate affected the basic or L-glutamate-inhibited synthesis of KYNA. It might be hypothesized that the impairment of KYNA production following the application of mGLU receptor agonists is related to their effects exerted upon the novel subtype of mGLU receptor.

Changes of kynurenic acid content in the rat and chicken retina during ontogeny

“…Glutamate has been shown to diminish KYNA synthesis in brain slices [39], and a regulatory influence of it on endogenous KYNA content has been suggested [40]. The decrease in retinal KYNA concentration found in our study during the first period of postnatal life might be explained by data of Haberecht and Redburn (1996), who reported a significant increase in the total rat retinal content of glutamate during the postnatal period in synchrony with the generation and maturation of glutamatergic cells [15].…”

Alterations of amino acids and glutamate transport in the DBA/2J mouse retina; possible clues to degeneration

“…It has previously been documented that glutamate diminished KYNA formation in brain slices [55] and a regulatory influence of glutamate on endogenous KYNA content has been suggested [56]. Therefore, it is possible that KYNA deficiency might result from the enhanced glutamatergic transmission observed in the present study.…”

Demonstration of Kynurenine Aminotransferases I and II and Characterization of Kynurenic Acid Synthesis in Oligodendrocyte Cell Line (OLN-93)

“…Glutamate, a potent inhibitor of KYNA synthesis in brain cortical (24,30) and spinal cord slices (25), astrocytes (29), and C6 cells (31), also significantly decreased KYNA production in oligodendrocytes. Selective agonist of ionotropic glutamate receptors AMPA, which was ineffective in attenuating KYNA synthesis either in neuronal tissue (25,30) or in astrocytes (29), decreased KYNA production in cultured oligodendrocytes, whereas one other selective agonist of ionotropic glutamate receptors -NMDA, had no influence on KYNA production.…”

“…Selective agonist of ionotropic glutamate receptors AMPA, which was ineffective in attenuating KYNA synthesis either in neuronal tissue (25,30) or in astrocytes (29), decreased KYNA production in cultured oligodendrocytes, whereas one other selective agonist of ionotropic glutamate receptors -NMDA, had no influence on KYNA production. This observation is consistent with the fact that immature oligodendrocytes express primarily the AMPA and kainate, but not the NMDA receptors (32).…”