Experimental Brain Research

, Volume 71, Issue 3, pp 563–567 | Cite as

On the disposition of intrahippocampally injected kynurenic acid in the rat

  • W. A. Turski
  • R. Schwarcz
Article

Summary

The disposition of kynurenic acid (KYNA), a tryptophan metabolite and broad spectrum antagonist at excitatory amino acid receptors, was studied following the unilateral intrahippocampal injection of 3H-KYNA in the rat. KYNA was rapidly cleared from the injected hippocampus. Similar decay curves were observed in several brain regions ipsi- and contralateral to the injection site as well as in serum and renal tissue. The radioactivity retained in tissue or excreted in urine for the first two hours after a 3H-KYNA injection was identified as unmetabolized KYNA. Moreover, direct measurement in hippocampal slices failed to provide evidence for the presence of specific cellular uptake mechanisms for KYNA. The present results do not support a neurotransmitter function for KYNA in the rat brain. However, they do not rule out a role of KYNA in the pathogenesis of neurodegenerative and seizure disorders.

Key words

Kynurenic acid Kynurenines Excitotoxins Neurodegenerative disorders Anticonvulsants 

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References

  1. Foster AC, Miller LP, Oldendorf WH, Schwarcz R (1984a) Studies on the disposition of quinolinic acid after intracerebral or systemic administration in the rat. Exp Neurol 84: 428–440Google Scholar
  2. Foster AC, Vezzani A, French ED, Schwarcz R (1984b) Kynurenic acid blocks neurotoxicity and seizures induced in rats by the related brain metabolite quinolinic acid. Neurosci Lett 48: 273–278Google Scholar
  3. Ganong AH, Lanthorn TH, Cotman CW (1983) Kynurenic acid inhibits synaptic and amino acid-induced responses in the rat hippocampus and spinal cord. Brain Res 273: 170–174Google Scholar
  4. Herrling PL (1985) Pharmacology of the corticocaudate excitatory postsynaptic potential in the cat: evidence for its mediation by quisqualate- or kainate receptors. Neuroscience 14: 417–426Google Scholar
  5. Minatogawa Y, Noguchi T, Kido R (1974) Kynurenine pyruvate transaminase in rat brain. J Neurochem 23: 271–272Google Scholar
  6. Monaghan DT, Cotman CW (1986) Anatomical organization of NMDA, kainate and quisqualate receptors. In: Roberts PJ, Storm-Mathisen J, Bradford HF (eds) Excitatory amino acids. Macmillan, London, pp 279–299Google Scholar
  7. Nakamura M, Turski WA, Whetsell WO Jr, Schwarcz R (1987) Identification of a kynurenate-like substance in human brain tissue. Soc Neurosci Abstr 13: 415.8Google Scholar
  8. Noguchi T, Minatogawa Y, Okuno E, Nakatani M, Morimoto M, Kido R (1975) Purification and characterization of kynurenine-2-oxoglutarate aminotransferase from the liver, brain and small intestine of rats. Biochem J 151: 399–406Google Scholar
  9. Perkins MN, Stone TW (1982) An iontophoretic investigation of the actions of convulsant kynurenines and their interaction with the endogenous excitant quinolinic acid. Brain Res 247: 183–187Google Scholar
  10. Schlossberger HG, Kochen W, Linzen B, Steinhart H (eds) (1984) Progress in tryptophan and serotonin research. De Gruyter, BerlinGoogle Scholar
  11. Schwarcz R, Whetsell WO Jr, Turski WA (1988) Kynurenines and nerve cell death. In: Nappi G, Agnoli A, Fariello R, Hornykiewicz O, Klawans H (eds) Neurotoxicity: basic and clinical research. Raven Press, New York (in press)Google Scholar
  12. Speciale C, Turski WA, Brookes N, Schwarcz R (1987) Sodiumdependent uptake of L-kynurenine into slices from rat brain. Soc Neurosci Abstr 13: 464.17Google Scholar
  13. Takahashi H, Kaihara M, Price JM (1956) The conversion of kynurenic acid to quinaldic acid by humans and rats. J Biol Chem 223: 705–708Google Scholar
  14. Turski L, Meldrum BS, Collins JF (1985a) Anticonvulsant action of β-kainic acid in mice. Is β-kainic acid an N-methyl-D-aspartate antagonist? Brain Res 336: 162–166Google Scholar
  15. Turski L, Schwarz M, Turski WA, Klockgether T, Sontag K-H, Collins JF (1985b) Muscle relaxant action of excitatory amino acid antagonists. Neurosci Lett 53: 321–326Google Scholar
  16. Turski WA, Schwarcz R (1987) On the disposition of intrahippocampally injected 3H-kynurenic acid in the rat. Soc Neurosci Abstr 13: 464.19Google Scholar

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • W. A. Turski
    • 1
  • R. Schwarcz
    • 1
  1. 1.Maryland Psychiatric Research CenterBaltimoreUSA

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