Kynurenic acid production in cultured bovine aortic endothelial cells. Homocysteine is a potent inhibitor

Kynurenic acid (KYNA) is a broad-spectrum antagonist at all subtypes of ionotropic glutamate receptors, but is preferentially active at the strychnine-insensitive glycine allosteric site of the N-methyl-d-aspartate (NMDA) receptor and is also a non-competitive antagonist at the alpha7 nicotinic receptor. KYNA occurs in the CNS, urine, serum and amniotic fluid. Whilst it possesses anticonvulsant and neuroprotective properties in the brain, its role in the periphery, however, is unknown. In this study we demonstrated the presence of kynurenine aminotransferase (KAT) I and II in the cytoplasm of bovine aortic endothelial cells (BAEC). BAEC incubated in the presence of the KYNA precursor l-kynurenine synthesized KYNA concentration- and time-dependently. KYNA production was inhibited by the aminotransferase inhibitor aminooxyacetic acid but was not affected by a depolarising concentration of K+ or by 4-aminopyridine. The glutamate agonists l-aspartate and l-glutamate depressed KYNA production significantly. The selective ionotropic glutamate receptor agonists α-amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropionic acid (AMPA) and NMDA were ineffective in this respect. d,l-Homocysteine and l-homocysteine sulphinic acid lowered KYNA production in BAEC. Further investigations are needed to assess the role and importance of KYNA in vessels and peripheral tissues.