Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1988 Apr;93(4):868–876. doi: 10.1111/j.1476-5381.1988.tb11474.x

Quinolinic acid effects on amino acid release from the rat cerebral cortex in vitro and in vivo.

J H Connick 1, T W Stone 1
PMCID: PMC1853900  PMID: 2898959

Abstract

1. The effect of quinolinic acid, N-methyl-D,L-aspartate (NMDLA) and kainate on the release of endogenous and exogenous amino acids from the rat cerebral cortex in vitro and in vivo was studied. 2. Neither quinolinic acid nor NMDLA had any effect on the basal or potassium-evoked release of [3H]-D-aspartate from slices of rat cerebral cortex either in the presence or absence of magnesium. Kainic acid failed to modify the basal efflux of [3H]-D-aspartate but significantly inhibited (by 34.4% +/- 0.04%, P less than 0.05) the potassium-evoked release. 3. Neither quinolinate nor NMDLA had any effect on the basal efflux of endogenous amino acids from rat cortical slices either in the presence or absence of magnesium ions at concentrations between 10 microM and 5 mM. 4. Both NMDLA (1 mM) and quinolinate (5 mM) produced an efflux of endogenous aspartate (371.4% +/- 11.6%; 389.3% +/- 12.1%) and glutamate (405.4% +/- 13.6%; 430.1 +/- 8.7%) respectively from the rat cerebral cortex in vivo (P less than 0.01). The quinolinic acid-evoked efflux was abolished by the NMDLA antagonist, 2-amino-5-phosphonovaleric acid (200 microM). 5. Kainic acid also caused an efflux of endogenous amino acids from the rat cerebral cortex in vivo. However, the profile of this release was different from that produced by quinolinate and NMDLA. 6. The results add further support to the suggestion that quinolinic acid acts at the NMDLA-preferring receptor and may also explain the requirement for intact afferent projections for the neurotoxic effects of quinolinate to be manifested.

Full text

PDF
868

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Addae J. I., Stone T. W. Effects of topically applied excitatory amino acids on evoked potentials and single cell activity in rat cerebral cortex. Eur J Pharmacol. 1986 Mar 4;121(3):337–343. doi: 10.1016/0014-2999(86)90254-2. [DOI] [PubMed] [Google Scholar]
  2. Clark R. M., Collins G. G. The release of endogenous amino acids from the rat visual cortex. J Physiol. 1976 Nov;262(2):383–400. doi: 10.1113/jphysiol.1976.sp011600. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Connick J. H., Stone T. W. The effect of kainic, quinolinic and beta-kainic acids on the release of endogenous amino acids from rat brain slices. Biochem Pharmacol. 1986 Oct 15;35(20):3631–3635. doi: 10.1016/0006-2952(86)90636-2. [DOI] [PubMed] [Google Scholar]
  4. Evans R. H., Francis A. A., Watkins J. C. Selective antagonism by Mg2+ of amino acid-induced depolarization of spinal neurones. Experientia. 1977 Apr 15;33(4):489–491. doi: 10.1007/BF01922227. [DOI] [PubMed] [Google Scholar]
  5. Evans R. H., Smith D. A. Effect of urethane on synaptic and amino acid-induced excitation in isolated spinal cord preparations. Neuropharmacology. 1982 Sep;21(9):857–860. doi: 10.1016/0028-3908(82)90076-4. [DOI] [PubMed] [Google Scholar]
  6. Fagg G. E., Lane J. D. The uptake and release of putative amino acid neurotransmitters. Neuroscience. 1979;4(8):1015–1036. doi: 10.1016/0306-4522(79)90185-4. [DOI] [PubMed] [Google Scholar]
  7. Ferkany J. W., Coyle J. T. Kainic acid selectively stimulates the release of endogenous excitatory acidic amino acids. J Pharmacol Exp Ther. 1983 May;225(2):399–406. [PubMed] [Google Scholar]
  8. Greenamyre J. T., Olson J. M., Penney J. B., Jr, Young A. B. Autoradiographic characterization of N-methyl-D-aspartate-, quisqualate- and kainate-sensitive glutamate binding sites. J Pharmacol Exp Ther. 1985 Apr;233(1):254–263. [PubMed] [Google Scholar]
  9. Jacobson I., Hamberger A. Kainic acid-induced changes of extracellular amino acid levels, evoked potentials and EEG activity in the rabbit olfactory bulb. Brain Res. 1985 Dec 2;348(2):289–296. doi: 10.1016/0006-8993(85)90447-0. [DOI] [PubMed] [Google Scholar]
  10. Jacobson I., Hamberger A. Veratridine-induced release in vivo and in vitro of amino acids in the rabbit olfactory bulb. Brain Res. 1984 May 7;299(1):103–112. doi: 10.1016/0006-8993(84)90792-3. [DOI] [PubMed] [Google Scholar]
  11. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  12. Lapin I. P. Kynurenines and seizures. Epilepsia. 1981 Jun;22(3):257–265. doi: 10.1111/j.1528-1157.1981.tb04108.x. [DOI] [PubMed] [Google Scholar]
  13. Lehmann A., Isacsson H., Hamberger A. Effects of in vivo administration of kainic acid on the extracellular amino acid pool in the rabbit hippocampus. J Neurochem. 1983 May;40(5):1314–1320. doi: 10.1111/j.1471-4159.1983.tb13572.x. [DOI] [PubMed] [Google Scholar]
  14. Lehmann A., Lazarewicz J. W., Zeise M. N-Methylaspartate-evoked liberation of taurine and phosphoethanolamine in vivo: site of release. J Neurochem. 1985 Oct;45(4):1172–1177. doi: 10.1111/j.1471-4159.1985.tb05538.x. [DOI] [PubMed] [Google Scholar]
  15. Lehmann J., Schaefer P., Ferkany J. W., Coyle J. T. Quinolinic acid evokes [3H]acetylcholine release in striatal slices: mediation by NMDA-type excitatory amino acid receptors. Eur J Pharmacol. 1983 Dec 9;96(1-2):111–115. doi: 10.1016/0014-2999(83)90536-8. [DOI] [PubMed] [Google Scholar]
  16. McGeer P. L., McGeer E. G. Kainic acid: The neurotoxic breakthrough. Crit Rev Toxicol. 1982 Mar;10(1):1–26. doi: 10.3109/10408448209033629. [DOI] [PubMed] [Google Scholar]
  17. Perkins M. N., Stone T. W. In vivo release of [3H]-purines by quinolinic acid and related compounds. Br J Pharmacol. 1983 Oct;80(2):263–267. doi: 10.1111/j.1476-5381.1983.tb10029.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Richelson E., Thompson E. J. Transport of neurotransmitter precursors into cultured cells. Nat New Biol. 1973 Feb 14;241(111):201–204. doi: 10.1038/newbio241201a0. [DOI] [PubMed] [Google Scholar]
  19. Roth M. Fluorescence reaction for amino acids. Anal Chem. 1971 Jun;43(7):880–882. doi: 10.1021/ac60302a020. [DOI] [PubMed] [Google Scholar]
  20. Schwarcz R., Foster A. C., French E. D., Whetsell W. O., Jr, Köhler C. Excitotoxic models for neurodegenerative disorders. Life Sci. 1984 Jul 2;35(1):19–32. doi: 10.1016/0024-3205(84)90148-6. [DOI] [PubMed] [Google Scholar]
  21. Schwarcz R., Whetsell W. O., Jr, Mangano R. M. Quinolinic acid: an endogenous metabolite that produces axon-sparing lesions in rat brain. Science. 1983 Jan 21;219(4582):316–318. doi: 10.1126/science.6849138. [DOI] [PubMed] [Google Scholar]
  22. Stone T. W., Connick J. H. Quinolinic acid and other kynurenines in the central nervous system. Neuroscience. 1985 Jul;15(3):597–617. doi: 10.1016/0306-4522(85)90063-6. [DOI] [PubMed] [Google Scholar]
  23. Turnell D. C., Cooper J. D. Rapid assay for amino acids in serum or urine by pre-column derivatization and reversed-phase liquid chromatography. Clin Chem. 1982 Mar;28(3):527–531. [PubMed] [Google Scholar]
  24. Vezzani A., Ungerstedt U., French E. D., Schwarcz R. In vivo brain dialysis of amino acids and simultaneous EEG measurements following intrahippocampal quinolinic acid injection: evidence for a dissociation between neurochemical changes and seizures. J Neurochem. 1985 Aug;45(2):335–344. doi: 10.1111/j.1471-4159.1985.tb03993.x. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES