On the Disposition of De Novo Synthesized Quinolinic Acid in Rat Brain Tissue

  • C. Speciale
  • R. Schwarcz
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 294)


Because of the putative role of the cerebral metabolite and specific N-methyl-D-aspartate receptor agonist quinolinic acid (QUIN) in physiological and pathological processes in the brain (Schwarcz et al., 1984; Stone and Burton, 1989; Lapin et al., this volume), the mechanisms by which QUIN function is regulated in the normal and diseased brain have become the object of investigative interest. The presence of 3-hydroxyanthranilic acid oxygenase (3HA0), QUIN’s immediate biosynthetic enzyme, in brain tissue (Foster et al., 1986b) indicated the possibility to assess the dynamics of QUIN disposition in whole cell preparations (tissue slices) which had been exposed to the substrate of 3HA0, 3-hydroxyanthranilic acid (3HANA). Preliminary experiments showed that QUIN can indeed be recovered from both tissue and incubation medium after the administration of 3HANA to slices from rat liver or brain in a physiological milieu (Speciale et al., 1989). Assay parameters have now been scrutinized in detail and optimal conditions for the examination of QUIN function in vitro have been established (Speciale et al., submitted for publication). In the present report, we describe the use of this experimental system for the initial assessment of mechanisms of QUIN release in normal and lesioned rat brain.


Quinolinic Acid Extracellular Compartment Ibotenic Acid Striatal Slice Basal Ganglion Lesion 
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  1. Foster, A.C., Okuno, E., Brougher, D.S., and Schwarcz, R., 1986a, A radio-enzymatic assay for quinolinic acid, Anal. Biochem., 158: 98–103.PubMedCrossRefGoogle Scholar
  2. Foster, A.C., White, R.J., and Schwarcz, R., 1986b, Synthesis of quinolinic acid by 3-hydroxyanthranilic acid oxygenase in rat brain tissue in vitro. J. Neurochem., 47: 23–30.PubMedCrossRefGoogle Scholar
  3. Köhler, C., Eriksson, L.G., Okuno, E., and Schwarcz, R., 1988, Localization of quinolinic acid metabolizing enzymes in the rat brain. Immunohisto-chemical studies using antibodies to 3-hydroxyanthranilic acid oxygenase and quinolinic acid phosphoribosyltransferase, Neuroscience 27: 49–76.PubMedCrossRefGoogle Scholar
  4. Schwarcz, R., Foster, A.C., French, E.D., Whetsell Jr., W.O., and Köhler, C., 1984, Excitotoxic models for neurodegenerative disorders, Life Sci., 35: 19–32.PubMedCrossRefGoogle Scholar
  5. Schwarcz, R., Hökfelt, T., Fuxe, K., Jonsson, G., Goldstein, M., and Terenius, L., 1979, Ibotenic acid induced neuronal degeneration: a morphological and neurochemical study, Exp. Brain Res., 37: 199–216.PubMedCrossRefGoogle Scholar
  6. Schwarcz, R., Okuno, E.,and White, R.J., 1989, Basal ganglia lesions in the rat: effects on quinolinic acid metabolism, Brain Res., 490: 103–109.PubMedCrossRefGoogle Scholar
  7. Speciale, C., Ungerstedt, U., and Schwarcz, R., 1989, Production of extracellular quinolinic acid in the striatum studied by microdialysis in unanes-thetized rats, Neurosci. Lett., 104: 345–350.PubMedCrossRefGoogle Scholar
  8. Stone, T.W., and Burton, N.R., 1988, NMDA receptors and ligands in the vertebrate CNS, Prog. Neurobiol., 10: 333–368.CrossRefGoogle Scholar
  9. Todd, W.P., Carpenter, B.K., and Schwarcz, R., 1989, Preparation of 4-halo-3-hydroxyanthranilates and demonstration of their inhibition of 3-hydroxy-anthranilate oxygenase in rat and human brain tissue, Prep. Biochem., 19: 155–165.PubMedCrossRefGoogle Scholar
  10. Wong, E.H., Kemp, J.A., Priestley, T., Knight, A.R., Woodruff, G.N., and Iversen, L.L., 1986, The novel anticonvulsant MK 801 is a potent N-methyl-D-aspartate antagonist, Proc. Nat. Acad. Sci. USA, 83: 7104–7108.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • C. Speciale
    • 1
  • R. Schwarcz
    • 1
  1. 1.Maryland Psychiatric Research CenterBaltimoreUSA

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