Skip to main content
SpringerLink
Log in

The selective inhibition of hippocampal glutamic acid decarboxylase in zinc-induced epileptic seizures

  • Original Articles
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

The intracerebroventricular administration of Zn2+ (0.3 μmol/10 μl) causes epileptic seizures characterized by running fits, jumping, vocalization, fasiculation of facial muscles, myoclonic movements of the limbs and tonic-clonic convulsions. These episodes are blocked or reversed by γ-aminobutyric acid (0.4 μmol/10 μl). When assayed under conditions where pyridoxal phosphate was not added, the activity of glutamic acid decarboxylase decreased significantly in hippocampus from 18.9 to 15.3 and 9.7 μmol14CO2 formed/gram proteins/20 min, 15 and 30 min following administration of Zn2+. The inhibition of glutamic acid decarboxylase by Zn2+ was selective occurring only in hippocampus and not in the hypothalamus, amygdala, caudate or thalamus. The inhibition of glutamic acid decarboxylase was not due to a reduction in the concentration of endogenous pyridoxal phosphate which remained unaltered in hippocampus following Zn2+ administration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Roberts, E., Chase, T. N., andTower, D. B. 1976. GABA in Nervous System Function. KROC Fdn. Series Vol. 5, Raven Press, New York.

    Google Scholar 

  2. Morselli, P. L., Lloyd, K. G., Löscher, W., Meldrum, B., andReynolds, E. H. 1981. Neurotransmitters, Seizures and Epilepsy. Raven Press, New York.

    Google Scholar 

  3. VanGelder, N. M., Sherwin, A. L., andRasmussen, T. 1972. Amino acid content of epileptogenic human brain: Focal versus surrounding regions. Brain Res. 40:385–393.

    PubMed  Google Scholar 

  4. VanGelder, N. M., andCourtois, A. 1972. Close correlation between changing content of specific amino acids in epileptogenic cortex of cats and severity of epilepsy. Brain Res. 43:477–484.

    PubMed  Google Scholar 

  5. Emson, P. C., andJoseph, M. H. 1975. Neurochemical and morphological changes during the development of cobalt-induced epilepsy in the rat. Brain Res. 93:91–110.

    PubMed  Google Scholar 

  6. Ribak, C. R., Harris, A. B., Vaughn, J. E., andRoberts, E. 1979. Inhibitory GABAergic nerve terminals decrease at sites of focal epilepsy. Sci. 205:211–214.

    Google Scholar 

  7. Bakay, R. A. E., andHarris, A. B. 1981. Neurotransmitter, receptor and biochemical changes in monkey cortical epileptic foci. Brain Res. 206:387–404.

    PubMed  Google Scholar 

  8. Roberts, E., andKuriyama, K. 1968. Biochemical-physiological correlations in studies of the γ-aminobutyric acid. Brain Res. 8:1–35.

    PubMed  Google Scholar 

  9. Kuriyama, K., Haber, T., Sisken, T., andRoberts, E. 1966. The γ-aminobutyric acid system in rabbit cerebellum. Proc. Nat. Acad. Sci., U.S.A. 55:846–849.

    Google Scholar 

  10. Kuriyama, K., Sisken, T., Haber, B., andRoberts, E. 1968. The γ-aminobutyric acid system in rabbit retina. Brain Res. 9:165–168.

    PubMed  Google Scholar 

  11. Fonum, F. 1975. The localization of glutamate decarboxylase, choline acetyltransferase and aromatic amino acid decarboxylase in mammalian and invertebrate nervous tissue. Pages 99–122,in Berl, S., Clark, D. D. andSchneider, D. (eds), Metabolic Compartmentation and Neurotransmission, Plenum Press, New York.

    Google Scholar 

  12. Roberts, E., Wein, J., andSimonsen, D. G. 1964. γ-aminobutyric acid (GABA), vitamin B6, and neuronal function—a speculative synthesis. Vitam. Horm. 22:503–559.

    PubMed  Google Scholar 

  13. Perez De La Mora, M., Feria-Velasco, A., andTapia, R. 1973. Pyridoxal phosphate and glutamate decarboxylase in subcellular particles of mouse brain and their relationship to convulsions. J. Neurochem. 20:1575–1587.

    PubMed  Google Scholar 

  14. Miller, L. P., Martin, D. L., Mazumder, A., andWaiters, J. P. 1978. Studies on the regulation of GABA synthesis: substrate-promoted dissociation of pyridoxal-5′-phosphate from GAD. J. Neurochem. 30:361–369.

    PubMed  Google Scholar 

  15. Ebadi, M. 1981. Regulation and function of pyridoxal phosphate in CNS. Neurochem. Int. 3:181–206.

    Google Scholar 

  16. Sytinsky, I. A., Soldatenkov, A. T., andLajtha, A. 1978. Neurochemical basis of the therapeutic effect of γ-aminobutyric acid and its derivatives. Prog. Neurobiol. 10:89–133.

    PubMed  Google Scholar 

  17. Donaldson, T., St.-Pierre, T., Minnich, J., andBarbeau, A. 1971. Seizures in rats associated with divalent cation inhibition of Na+K+-ATPase. Can. J. Biochem. 49:1217–1224.

    Google Scholar 

  18. Wu, J.-Y., andRoberts, E. 1974. Properties of brainl-glutamate decarboxylase-inhibition studies. J. Neurochem. 23:759–767.

    PubMed  Google Scholar 

  19. Wu, J.-Y., Wong, E., Saito, K., Roberts, E., andSchousboe, A. 1976. Properties of L-glutamate decarboxylase from brains of adult and newborn mice. J. Neurochem. 27:653–659.

    PubMed  Google Scholar 

  20. McCormick, D. B., Gregory, M. E., andSnell, E. E. 1961. Pyridoxal phosphokinases—I. Assay, distribution, purification and properties. J. Biol. Chem. 236:2076–2084.

    PubMed  Google Scholar 

  21. Neary, J. T., andDiven, W. F. 1970. Purification, properties and a possible mechanism for pyridoxal kinase from bovine brain. J. Biol. Chem. 245:5585–5593.

    PubMed  Google Scholar 

  22. Ebadi, M., Itoh, M., Bifano, J., Wendt, K., andEarle, A. 1981. The role of Zn++ in pyridoxal phosphate mediated regulation of glutamic acid decarboxylase in brain. Int. J. Biochem. 13:1107–1112.

    PubMed  Google Scholar 

  23. Itoh, M., andEbadi, M. 1981. The selective inhibition of glutamic acid decarboxylase (GAD) in hippocampus by Zn++. Pharmacologist 23:243.

    Google Scholar 

  24. Sundaresan, P. R., andCoursin, D. B. 1970. Microassay of pyridoxal phosphate usingl-tyrosine-[14C] and tyrosine apodecarboxylase. Pages 509–512,in McCormick, D. B. andWright, L. B. (eds) Methods in Enzymology, Vol. 18, Academic Press, New York.

    Google Scholar 

  25. Bhagavan, H. M., Koogler, H. M. Jr. andCoursin, D. B. 1976. Enzymatic microassay of pyridoxal-5-phosphate using L-tyrosine apodecarboxylase andl-[1-14C]tyrosine. Int. J. Vitam. Nutr. Res. 46:160–164.

    PubMed  Google Scholar 

  26. Smeyers-Verbeke, J., DeFrise-Gussenhoven, E., Ebinger, G., Lowenthal, A., andMassart, D. L. 1974. Distribution of Cu and Zn in human brain tissue. Clinica Chim. Acta 51:309–314.

    Google Scholar 

  27. Wuyts, L., Smeyers-Verbeke, J., andMassart, D. L. 1976. Atomic absorption spectrophotometry of copper and zinc in human brain tissue. A critical investigation of two digestion techniques. Clinica. Chim. Acta 72:405–407.

    Google Scholar 

  28. Noble, E. P., Wurtman, R. J., andAxelrod, J. 1967. A simple and rapid method for injecting H3-norepinephrine into the lateral ventricle of the rat brain. Life Sci. 6:281–291.

    PubMed  Google Scholar 

  29. Glowinski, J., andIversen, L. L. 1966. Regional studies of catecholamines in the rat brain—I. The disposition of [3H] norepinephrine, [3H]dopamine and [3H]dopa in various regions of the brain. J. Neurochem. 13:655–669.

    PubMed  Google Scholar 

  30. König, F. R., andKlippel, R. A. 1963. The Rat Brain. William and Wilkins, Baltimore.

    Google Scholar 

  31. Lowry, O. H., Rosebrough, N. J., Farr, A. L., andRandall, R. J. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193:265–275.

    PubMed  Google Scholar 

  32. Armitage, P. 1971. Statistical Methods in Medical Research. Wiley, New York.

    Google Scholar 

  33. Storm-Mathisen, J. 1972. Glutamate decarboxylase in the rat hippocampal region after lesions of the afferent fibre systems. Brain Res. 40:215–235.

    PubMed  Google Scholar 

  34. Andersen, P., Eccles, J. C., andLøyning, Y. 1964. Pathways of postsynaptic inhibition in the hippocampus. J. Neurophysiol. 27:608.

    PubMed  Google Scholar 

  35. Biscoe, T. J., andStraughan, D. W. 1966. Micro-electrophoretic studies of neurones in the cat hippocampus. J. Physiol. (Lond.) 183:341.

    Google Scholar 

  36. Curtis, D. R., Felix, D., andMcLennan, H. 1970. GABA and hippocampal inhibition. Br. J. Pharmacol. 40:881–883.

    PubMed  Google Scholar 

  37. Itoh, M., andUchimura, H. 1981. Regional Differences in Cofactor Saturation of Glutamate Decarboxylase (GAD) in Discrete Brain Nuclei of the Rat: Effect of Repeated Administration of Haloperidol on GAD Activity in the Substantia Nigra. Neurochem. Res. 6:1283–1289.

    PubMed  Google Scholar 

  38. Bayon, A., Possani, L. D., andTapia, R. 1977. Kinetics of brain glutamate decarboxylase—inhibition studies with N-(5′-phosphopyridoxal) amino acids. J. Neurochem. 29:513–517.

    PubMed  Google Scholar 

  39. Bayon, A., Possani, L. D., Tapia, M., andTapia, R. 1977. Kinetics of brain glutamate decarboxylase. Interactions with glutamate, pyridoxal 5-phosphate and glutamine-pyridoxal 5-phosphate. Schiff base. J. Neurochem. 29:519–525.

    PubMed  Google Scholar 

  40. Covarrubias, M., andTapia, R. 1980. Brain glutamate decarboxylase: properties of its calcium-dependent binding to liposomes and kinetics of the bound and the free enzyme. J. Neurochem. 34:1682–1688.

    PubMed  Google Scholar 

  41. Prasad, A. S. 1979. Clinical, biochemical and pharmacological role of zinc. A Rev. Pharmac. Toxic. 20:393–426.

    Google Scholar 

  42. Itoh, M. andEbadi, M. 1982. Zinc binding proteins in rat brain and their interactions with glutamic acid decarboxylase. Fed. Proc. 41:8736.

    Google Scholar 

Download references

Author information

Author notes

  1. Masatoshi Itoh M.D.

    Present address: Department of Neuropsychiatry, Faculty of Medicine, Kyushu University, 60, Maidashi 3-1-1, 812, Fukuoka, Japan

Authors and Affiliations

  1. Department of Pharmacology, The University of Nebraska College of Medicine, 42nd Street and Dewey Avenue, 68105, Omaha, Nebraska

    Masatoshi Itoh M.D. & Manuchair Ebadi

Authors
  1. Masatoshi Itoh M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Manuchair Ebadi
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Itoh, M., Ebadi, M. The selective inhibition of hippocampal glutamic acid decarboxylase in zinc-induced epileptic seizures. Neurochem Res 7, 1287–1298 (1982). https://doi.org/10.1007/BF00965899

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00965899

Keywords

Search

Navigation