The Regulation of Brain Kynurenic Acid Content: Focus on Indole-3-Pyruvic Acid

  • F. Moroni
  • P. Russi
  • V. Carlà
  • G. De Luca
  • V. Politi
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 294)


The actual interest in the role that kynurenic acid (KYNA), one of the first identified metabolic products of tryptophan, (Ellinger et al., 1904 in Heidelberger et al., 1949; see Fig. 1) may have in physiology or pathology stems from at least three groups of observations. First, KYNA antagonizes in a non-competitive manner excitatory amino acid (EAA) receptors (Perkins and Stone, 1982; Moroni et al., 1986); second, it prevents the excitotoxic actions of the related tryptophan (TRP) metabolite quinolinic acid (QUIN) (Foster et al., 1984) and reduces neuronal damage after anoxic and ischemic brain insults (Germano et al., 1987); and third, it is present in mammalian biological fluids and in the central nervous system (Moroni et al., 1988b).


Excitatory Amino Acid Quinolinic Acid Kynurenic Acid Excitatory Amino Acid Receptor Brain Content 
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  1. Bacciottini, L., Pellegrini-Giampietro, D., Bongianni, F., De Luca, G., Beni, M., Politi, V., and Moroni, F., 1987, Biochemical and behavioural studies on indole-pyruvic acid: a keto analogue of tryptophan, Pharmacol. Res. Comm., 19: 803–807.CrossRefGoogle Scholar
  2. Carlà, V., Lombardi, G., Beni, M., Russi, P., Moneti, G., and Moroni, F., 1988, Identification and measurement of kynurenic acid in the rat brain and other organs, Anal. Biochem., 169: 89–94.PubMedCrossRefGoogle Scholar
  3. Foster, A.C., Vezzani, A.M., French, E.D., and Schwarcz, R., 1984, Kynurenic acid blocks neurotoxicity and seizures in rats by the related brain metabolite quinolinic acid, Neurosci. Lett., 48: 273–278.PubMedCrossRefGoogle Scholar
  4. Gàl, E.M., Young, R.B., and Sherman, A.D., 1978, Tryptophan loading: consequent effects on the synthesis of kynurenine and 5-hydroxyndoles in rat brain, J. Neurochem., 31: 237–244.PubMedCrossRefGoogle Scholar
  5. Germano, I.M., Pitts, L.H., Meldrum, B.S., Bartkowski, H.M., and Simon, R.P., 1987, Kynurenate inhibition of cell excitation decreases stroke size and deficits, Ann. Neurol., 22: 730–734.PubMedCrossRefGoogle Scholar
  6. Heidelberger, C., Guldberg, M.E., Morgan, A.F., and Lepkovsky, S., 1949, Tryptophan metabolism I: concerning the mechanism of the mammalian conversion of tryptophan into kynurenine, kynurenic acid and nicotinic acid, J. Biol. Chem., 179: 143–150.PubMedGoogle Scholar
  7. Johnson, J.W., and Ascher, P., 1987, Glycine potentiates the NMDA response in cultured mouse brain neurones, Nature, 325: 529–531.PubMedCrossRefGoogle Scholar
  8. Kemp, J.A., Foster, A.C., Leeson, P.D., Priestley, T., Tridgett, R., Iversen, L.L., and Woodruff, G.N., 1988, 7-Chlorokynurenic acid is a selective antagonist at the glycine modulatory site of the N-methyl-D-aspartate receptor complex, Proc. Natl. Acad. Sci. USA, 85: 6547–6550.PubMedCrossRefGoogle Scholar
  9. Kuroda, Y., 1950, A contribution to the metabolism of tryptophan, J. Biochem., 37: 91–97.Google Scholar
  10. Millard, A., and Gál, E.M., 1971, The contribution of 5-hydroxyindole-pyruvic acid to cerebral 5-hydroxyindole metabolism, Int. J. Neurosci., 1: 211–218.PubMedCrossRefGoogle Scholar
  11. Moroni, F., Lombardi, G., Carlà, V., and Moneti, G., 1984, The excitotoxin quinolinic acid is present and unevenly distributed in the rat brain, Brain Res., 295: 352–355.PubMedCrossRefGoogle Scholar
  12. Moroni, F., Luzzi, S., Franchi-Micheli, S., and Zilletti, L., 1986, The presence of NMDA-type receptors for glutamic acid in the guinea pig myenteric plexus, Neurosci. Lett., 68: 57–62.PubMedCrossRefGoogle Scholar
  13. Moroni, F., Pellegrini-Giampietro, D.E., Alesiani, M., Cherici, G., Mori, F., and Galli, A., 1989, Glycine and kynurenate modulate the glutamate receptors present in the myenteric plexus and in cortical membranes, Eur. J. Pharmacol., 163: 123–126.PubMedCrossRefGoogle Scholar
  14. Moroni, F., Russi, P., Carlà, V., and Lombardi, G., 1988a, Kynurenic acid is present in the rat brain and its content increases during development and aging processes, Neurosci. Lett., 94: 145–150.PubMedCrossRefGoogle Scholar
  15. Moroni, F., Russi, P., Lombardi, G., Beni, M., Carlà, V., 1988b, Presence of kynurenic acid in the mammalian brain, J. Neurochem., 51: 177–180.PubMedCrossRefGoogle Scholar
  16. Morris, R.G.M., Andersen, E., Lynch, G.S., and Baudry, M., 1986, Selective impairment of learning and blockade of long term potentiation by an NMDA antagonist, Nature, 319: 774–776.PubMedCrossRefGoogle Scholar
  17. Neff, N.H., Tozer, T.N., and Brodie, B.B., 1967, Application of steady-state kinetics to studies of the transfer of 5-HIAA from brain to plasma, J. Pharmacol. Exp. Ther., 158: 214–218.Google Scholar
  18. Pearce, I.A., Cambray-Dekin, M.A., and Burgoyne, R.D., 1987, Glutamate acting on NMDA receptors stimulates neurite outgrowth from cerebellar granule cells, FEBS Lett., 233: 143–147.CrossRefGoogle Scholar
  19. Perkins, M.N., and Stone, T.W., 1982, An iontophoretic investigation of the actions of convulsant kynurenines and the interaction with the endogenous excitant quinolinic acid, Brain Res., 247: 184–187.PubMedCrossRefGoogle Scholar
  20. Phillips, S.R., Durden, D.A., and Boulton, A.A., 1974, Identification and distribution of tryptamine in the rat, Can. J. Biochem., 52: 477–481.CrossRefGoogle Scholar
  21. Saavedra, J.M., and Axelrod, J., 1972, A specific and sensitive enzymatic essay for tryptamine in tissues, J. Pharmacol. Exp. Ther., 182: 363–369.PubMedGoogle Scholar
  22. Werner, E.R., Werner-Felmayer, G., Fuchs, D., Hausen, A., Reibnegger, G., and Wachter, H., 1988, Influence of interferon-gamma and extracellular tryptophan on indoleamine 2,3-dioxygenase activity in T24 cells as determined by a non-radiometric assay, Biochem. J., 256: 537–541.PubMedGoogle Scholar
  23. Yoshida, R., Urade, Y., Tokuda, M., and Hayaishi, O., 1979, Induction of indoleamine 2,3-dioxygenase in mouse lung during infection, Proc. Natl. Acad. Sci. USA, 76: 4084–4086.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • F. Moroni
    • 1
  • P. Russi
    • 1
  • V. Carlà
    • 1
  • G. De Luca
    • 2
  • V. Politi
    • 2
  1. 1.Department of PharmacologyUniversity of FlorenceItaly
  2. 2.Polifarma S.p.A.RomaItaly

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