Advertisement

Zinc-Binding Proteins in the Brain

  • M. Ebadi
  • Y. Hama
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 203)

Abstract

As an essential substance, zinc is involved in maintaining the functions and/or the structures of at least 200 metalloenzymes that participate in numerous biochemical reactions, including the metabolism of proteins and nucleic acids. The steady-state concentration of zinc in the brain must be regulated firmly since both an excess and a deficiency of zinc have been implicated in neurological disorders including epilepsy. Zinc-binding proteins have been detected in the bovine hippocampus, cerebellum, and pineal gland. A metallothionein-like protein has been identified recently in the rat brain which resembles in some but not all aspects a hepatic metallothionein. The synthesis of this protein is stimulated following the administration of zinc 40 copper but not of cadmium. The zinc-stimulated protein incorporates 35S cysteine 24-fold higher than the native, unstimulated protein; is blocked by actinomycin D; produces two isoforms by ion exchange chromatography on DEAE Sephadex A 25 columns; and by high performance liquid chromatography, depicts a similar but not identical profile to zinc-stimulated hepatic metallothionein. Since the synthesis of this protein is stimulated following the administration of zinc and is depressed in the brains of zinc-deficient rats, it is postulated that the unbound pool of zinc may serve as one of the factors involved in regulating the synthesis of this protein. Since zinc in physiological concentrations stimulates a number of pyridoxal phosphate-dependent reactions and in pharmacological doses inhibits an extensive number of SH-containing enzymes and receptor sites for neurotransmitters, we postulate that the metallothionein-like protein in the brain may have function(s) associated with zinc homeostasis and perhaps events related to synaptic functions.

Keywords

Zinc Deficiency Glutamic Acid Decarboxylase Zinc Sulfate Pyridoxal Phosphate S100b Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Alley, M.C., Killam, E.K., and Fisher, G.L., 1983, The influence of D-peni- cillamine treatment upon seizure activity and trace metal status in the Senegalese baboon, Pardo panic, J, Pharmacol. Exp. Ther., 217: 138.Google Scholar
  2. Awad, A., and Ebadi, M., 1985, The characteristics of metallothioneins in bovine pineal gland, Fed. Proc., 44: 3053.Google Scholar
  3. Baraldi, M., Caselgrandi, E., Borella, P., and Zeneroli, M.L., 1983, Decrease of brain zinc in experimental hepatic encephalopathy, Brain Res., 258: 170.CrossRefGoogle Scholar
  4. Bastek, J., Bogden, A., Cinotti, W., Tenhove, G., Stephans, M., Markopoulos, M., and Charles, J., 1976, Trace metals in a family with sex-linked retinitis pigmentosa, in: Retinitis Pigmentosa, M.B. Landers, III,M.L. Wolbarsht, J.E. Dowling and A.M. Latios, eds., Plenum Press, New York, p. 43.Google Scholar
  5. Baudier, J., and Gerard, D., 1983, Ions binding to 5100 proteins: structural changes induced by calcium and zinc on S100a and S100b proteins,Biochemistry, 22: 3360.PubMedCrossRefGoogle Scholar
  6. Baudier, J., Haglid, K., Haiech, J., and Gerard, D., 1983, Zinc ion binding to human brain calcium binding proteins, calmodulin and S100b protein, Biochem. Biophvs. Res. Comm., 114: 1138.CrossRefGoogle Scholar
  7. Baudier, J., Labourdette, G., and Gerard, D., 1985, Rat brain S100b protein: purification, characterization, and ion binding properties. A comparison with bovine S100b protein, J. Neurochem., 44: 76.PubMedCrossRefGoogle Scholar
  8. Ben-Ari, Y., and Krnjevié, K., 1981, Actions of GABA on hippocampal neurons with special reference to the aetiology of epilepsy, in: Neurotransmitters, Seizures, and Epilepsy, P.L. Morselli, K.G. Lloyd, W. Löscher,B. Meldrum and E.H. Reynolds, eds., Raven Press, New York, p. 63.Google Scholar
  9. Borges, L.F., and Gucer, d., 1978, Effect of magnesium on epileptic foci, Epilepsia, 19: 81.PubMedCrossRefGoogle Scholar
  10. Brewer, G.J., Aster, J.C., Knutsen, C.A., and Kruckeberg, W.C., 1979, Zinc inhibition of calmodulin: a proposed molecular mechanism of zinc action on cellular functions, Am. J. Hematol., 7: 53.PubMedCrossRefGoogle Scholar
  11. Brewer, G.J., Hill, G.M., Prasad, A.S., and Cossack, Z.T., 1983, Biological roles of ionic zinc, in: Zinc Deficiency in Human Subjects, A.S. Prasad, A.O. Cavdar, G.J. Brewer, and P.J. Aggett, eds., Alan R. Liss, Inc., New York, p. 35.Google Scholar
  12. Buell, S.J., Fosmire, G.J., 011erich, D.A., and Sandstead, H.H., 1977, Effects of postnatal zinc deficiency on cerebellar and hippocampal development in the rat, EXp. Neurol., 55: 199.PubMedCrossRefGoogle Scholar
  13. Chen, R.W., and Ganther, H.E., 1975, Relative cadmium binding capacity of metallothionein and other cytosolic fraction in various tissues of the rat, Environ. Physiol. Biochem., 5: 235.PubMedGoogle Scholar
  14. Chung, S.H., and Johnson, M.S., 1983, Divalent transition-metal ions (Cu2+ and Zn2+) in the brains of epileptogenic and normal mice, Brain Res., 280: 323.PubMedCrossRefGoogle Scholar
  15. Constantinidis, J., and Tissot, R., 1981, Role of glutamate and zinc in the hippocampal lesions of Pick’s disease, in: Glutamate as a Neurotransmitter, G. DiChiara and G.L. Gessa, eds., Raven Press, New York, p. 413.Google Scholar
  16. Cousins, R.J., 1985, Absorption, transport, and hepatic metabolism of copper and zinc: special reference to metallothionein and ceruloplasmin, Physiol. Rev., 65: 238.Google Scholar
  17. Crawford, I.L., and Harris, N.F., 1984, Distribution and accumulation of zinc in whole brain and subcellular fractions of hippocampal homogenates, in: The Neurobiology of Zinc, Part A. Physiochemistry, Anatomy and Techniques, C.J. Frederickson, G.A. Howell, and E.J. Kasarskis, eds., Alan R. Liss, Inc., New York, p. 157.Google Scholar
  18. Denner, L.A., and Wu, J.-Y., 1985, Two forms of rat brain glutamic acid decarboxylase differ in their dependence on free pyridoxal phosphate, J. Neurochem., 44: 957.PubMedCrossRefGoogle Scholar
  19. De Vries, D.J., and Beart, P.M., 1985, Competitive inhibition of [3H] spiperone binding to D-2 dopamine receptors in striatal homogenates by organic calcium channel antagonists and polyvalent cations, Eur. J. Pharmacol., 106: 133.CrossRefGoogle Scholar
  20. Donaldson, J., St. Pierre, T., Minnich, J.L., and Barbeau, A., 1971, Seizures in rats associated with divalent cation inhibiton of Na+K+ATPase, Can.J. Bioçhem., 49: 1217.Google Scholar
  21. Dore-Duffy, P., Catalanotto, F., Donaldson, J.O., Ostrom, K.M., and Testa, M.A., 1983, Zinc in multiple sclerosis, Ann. Neurol., 14: 450.PubMedCrossRefGoogle Scholar
  22. Dreosti, I.E., 1984, Zinc in the central nervous system: the emerging interactions, in: The Neurobiology of Zinc. Part A. Physiochemistry. Anatomy and Techniques, A.J. Frederickson, G.A. Howell, and E.J. Kasarskis, eds., Alan R. Liss, Inc., New York, p. 1.Google Scholar
  23. Dvergsten, C.L., Fosmire, G.J., 011erich, D.A., and Sandstead, H.H., 1983, Alterations in the postnatal development of the cerebellar cortex due to zinc deficiency. I. Impaired acquisition of granule cells, Brain Res., 271: 217.PubMedCrossRefGoogle Scholar
  24. Dvergsten, C.L., Fosmire, G.J., 011erich, D.A., and Sandstead, H.H., 1984a, Alterations in the postnatal development of the cerebellar cortex due to zinc deficiency. H. Impaired maturation of Purkinje cells, Dev. Brain Res., 16: 11.CrossRefGoogle Scholar
  25. Dvergsten, C.L., Johnson, L.A., and Sandstead, H.H., 1984b, Alterations in the postnatal development of the cerebellar cortex due to zinc deficiency. III. Impaired dendritic differentiation of basket and stellate cells, Dev, Brain Res., 16: 21CrossRefGoogle Scholar
  26. Ebadi, M Itoh, M., Bifano, J., Wendt, K., and Earle, A., 1981, The role of Zn1+ in pyridoxal phosphate-mediated regulation of glutamie acid decarboxylase in brain, Int. J. Bioçhem., 13: 1107.PubMedCrossRefGoogle Scholar
  27. Ebadi, M., 1984a, Characterization of zinc binding ligand in rat brain, Trans. Soc. Neurosci., 14: 1062.Google Scholar
  28. Ebadi, M., 1984b, The presence of metallothionein-like protein in rat brain, Fed. Proc., 43, 3317.Google Scholar
  29. Ebadi, M., and Pfeiffer, R.F., 1984, Zinc in neurological disorders and in experimentally induced epileptiform seizures, in: The Neurobiology of Zinc. Part B, Deficiency. Toxicity. and Pathology, C.J. Frederickson, G.A. Howell, and E.J. Kasarskis, eds., Alan R. Liss, Inc., New York,p. 307.Google Scholar
  30. Ebadi, M., White, R.J., and Swanson, S., 1984, The presence and functions of zinc binding proteins in developing and mature brains, in: Neurobiology of Zinc (Part A), C.J. Frederickson, G.A. Howell, and E.J. Kasarkis, eds., Alan R. Liss, Inc., New York, p. 39.Google Scholar
  31. Ebadi, M., 1985, The role of zinc in growth and development, J. Nutr. Growth and Cancer, 2: 181.Google Scholar
  32. Ebadi, M., and Wallwork, J.C., 1985, Zinc binding proteins (ligands) in brains of severely zinc deficient rats, Biol, Trace Element Res., 7: 129.CrossRefGoogle Scholar
  33. Ebadi, M., Babin, D., and Swanson, S., 1985, Amino acid analysis and HPLC characterization of the isoforms of the metallothionein-like protein in rat brain, Trans. Soc. Neurosci., 15: 155.Google Scholar
  34. Eckhert, C.D., 1981, Elevated body zinc in rats with inherited dystrophy, J. Heredity, 72: 130.Google Scholar
  35. Fujii, T., 1954,. Presence of zinc in nucleoli and its possible role in mitosis, Nature, 174: 1108.Google Scholar
  36. Goldberg, H.J., and Sheehy, E.M., 1982, Fifth day fits: an acute zinc deficiency syndrome?, Arch. Dis. Childh., 57: 632.CrossRefGoogle Scholar
  37. Golub, M.S., Gershwin, M.E., and Vijayan, V.K., 1983, Passive avoidance performance of mice fed marginally or severely zinc deficient diets during post-embryonic brain development, Physiol. Behay., 30: 409.CrossRefGoogle Scholar
  38. Gordon, E.F., 1984, Behavioral correlates of experimental zinc deficiency, in: The Neurobiology of Zinc. Part B. Deficiency, Toxicity, and Pathology, C.J. Frederickson, G.A. Howell, and E.J. Kasarskis, eds., Alan R. Liss, Inc., New York, p. 77.Google Scholar
  39. Govitrapong, P., Hama, Y., Awad, A., and Ebadi, M., 1985, The inhibitory action of zinc and cadmium on D2 dopamine and glutamate receptors in bovine pineal gland, Trans. Endocr. Soc., 67: 1272.Google Scholar
  40. Halas, E.S., and Sandstead, H.H., 1975, Some effects of prenatal zinc deficiency on behavior of the adult rat, Pediatric. Res., 9: 94.Google Scholar
  41. Halas, E.S., Hanlon, M.J., and Sandstead, H.H., 1975, Intrauterine nutri-tion and aggression, Nature, 257: 221.PubMedCrossRefGoogle Scholar
  42. Halas, E.S., Reynolds, G., Rowe, M., Heinrich, M., and Pirc, M., 1977, Comparison of frequency, intensity and duration of aggressive responses in rats, Physiol. Behay., 18: 975.CrossRefGoogle Scholar
  43. Halas, E.S., Heinrich, M.D., and Sandstead, H.H., 1979, Long term memory deficits in adult rats due to postnatal malnutrition, Physiol. Behay., 22: 991.CrossRefGoogle Scholar
  44. Halas, E.S., Eberhardt, J.J., Diers, M.A., and Sandstead, H.H., 1983, Learning and memory impairment in adult rats due to severe zinc deficiency during lactation, Physiol, Behay., 30: 371.CrossRefGoogle Scholar
  45. Halas, E.S., and Kawamoto, J.C., 1984, Correlated behavioral and hippocampal effects due to perinatal zinc deprivation, in: The Neurobiology of Zinc. Part B. Deficiency, Toxicity, and Pathology, C.J. Frederickson, G.A. Howell, and E.J. Kasarskis, eds., Alan R. Liss, Inc., New York, p. 91.Google Scholar
  46. Haug, F.-M.S., 1967, Electron microscopical localization of the zinc in hippocampal mossy fiber synapses by a modified sulphide silver procedure, Histochemistry, 8: 355.PubMedCrossRefGoogle Scholar
  47. Heilmaier, H.E., Summer, K.H., 1985, Metallothionein content and zinc status in various tissues of rats treated with iodoacetic acid and zinc, Arch. Toxicpl., 56: 247.CrossRefGoogle Scholar
  48. Hershey, C.O., Hershey, L.A., Varnes, A., Vibhakar, S.D., Lavin, P., and Strain, W.H., 1983, Cerebrospinal fluid trace element content in dementia:clinical, radiologie, and pathologic correlations, Neurology, 33: 1350.PubMedCrossRefGoogle Scholar
  49. Hesketh, J.E., 1983, Zinc binding to tubulin, Int. J. Biochem., 15: 743.PubMedCrossRefGoogle Scholar
  50. Hurley, L.S., Gowan, J., and Swenerton, H., 1971, Teratogenic effectsof short-term and transitory zinc deficiency in rats, Teratology, 4: 199.CrossRefGoogle Scholar
  51. Hurley, L.S., 1981, Teratogenic aspects of manganese, zinc, and copper nutrition, Physiol. Rev., 61: 249.PubMedGoogle Scholar
  52. Itoh, M., and Ebadi, M., 1982a, Zinc binding proteins in rat brain and their interactions with glutamic acid decarboxylase, Fed. Proc., 41: 9736.Google Scholar
  53. Itoh, M., and Ebadi, M., 1982b, The selective inhibition of hippocampal glutamic acid decarboxylase in zinc-induced epileptic seizures, Neuro-chem. Res., 7: 1287.Google Scholar
  54. Itoh, M., Ebadi, M., and Swanson, S., 1983, The presence of zinc binding proteins in brain, J. Neurochem., 41: 823.PubMedCrossRefGoogle Scholar
  55. Judd, A.M., MacLeod, R.M., and Login, I.S., 1984, Zinc acutely, selectively and reversibly inhibits pituitary prolactin secretion, Brain Res., 294: 190.PubMedCrossRefGoogle Scholar
  56. Kagi, J.H., and Vallee, B.L., 1960, Metallothionein: a cadmium- and zinc containing protein from equine renal cortex, J. Biol, Chem., 235: 3460.Google Scholar
  57. Kagi, J.H., and Nordberg, M., 1979, Metallothionein, Birkhäuser Verlag,Basel, Switzerland.Google Scholar
  58. Karin, M., and Richards, R.I., 1982, Human metallothionein genes-primary structure of the metallothionein-II gene and a related processed gene, Nature, 299: 797.PubMedCrossRefGoogle Scholar
  59. Kimura, K. and Kumura, J., 1965, Polarigraphic determination of zinc levels in the brains of schizophrenics and control patients, Proc. Jap. Acad., 41: 943.Google Scholar
  60. Klauser, S., Kagi, J.H.R., and Wilson, K.J., 1983, Characterization of isoprotein patterns in tissue extracts and isolated samples of metallothioneins by reverse-phase high pressure liquid chromatography, Biochem. J., 209: 71.PubMedGoogle Scholar
  61. Klee, M.R., and Lieflander, M., 1965, Über das Vorkommen von Zink und Carbonat-hydro-lyase im Kaninchenhirn, Hoppe Sevler’s Z, Phvsiol. Chem., 341:143.CrossRefGoogle Scholar
  62. Lee, C.-M., Javitch, J.A., and Snyder, S.H., 1983, 3H-Substance P binding to salivary gland membranes regulation by guanyl nucleotides and divalent cations, Mol. Pharmacol., 23: 563.PubMedGoogle Scholar
  63. Lindskog, S., 1983, Carbonic anhydrase, in: Zinc Enzymes, T.G. Spiro, ed., John Wiley and Sons, New York, p. 79.Google Scholar
  64. Login, I.S., Thorner, M.O., and MacLeod, R.M., 1983, Zinc may have a physiological role in regulating pituitary prolactin secretion, Neuroendocrinology, 37: 317.PubMedCrossRefGoogle Scholar
  65. Lucier, G.W., and Hook, G.E., 1984, Metallothionein and cadmium nephrotoxicity, in: Environmental Health Perspectives, 54, U.S. Government Printing Office, Washington, D.C.Google Scholar
  66. Majumdar, S.K., Shaw, G.K., and Thomson, A.D., 1983, Serum zinc, magnesium and calcium status in the Wernicke-Korsakoff syndrome, Drug and Alcohol Dependence, 12: 403.PubMedCrossRefGoogle Scholar
  67. Mizuno, S., Ogawa, N., and Mori, A., 1983, Differential effects of some transition metal cations on the binding of p-carboline-3-carboxylate and diazepam, Neurochem. Res., 8: 873.PubMedCrossRefGoogle Scholar
  68. Mozha, I.B., 1974, Levels of various trace elements in the blood of patients with various types of retinal pathology, Vestn. Oftalmol., 5: 59.Google Scholar
  69. Nair, V., and Bau, D., 1971, Studies on the functional significance of carbonic anhydrase in central nervous system, Brain Res., 31: 185.PubMedCrossRefGoogle Scholar
  70. Neve, J., Sinet, P.M., Molle, L., and Nicole, A., 1983, Selenium, zinc and copper in Down’s syndrome (trisomy 21): blood levels and relations with glutathione peroxidase and superoxide dismutase, Clin. Chim.Acta, 133: 209.PubMedCrossRefGoogle Scholar
  71. Nielson, K.B., and Winge, D.R., 1983, Order of metal binding in metallothionein, J. Biol. Chem., 258: 13063.PubMedGoogle Scholar
  72. O’Dell, B.L., 1974, Role of zinc in protein synthesis, in: Clinical Applications of Zinc Metabolism, W.J. Pories, W.H. Strain, J.M. Hsu, and R.L. Woosley, eds., Charles C. Thomas, Springfield, p. 5.Google Scholar
  73. Olton, D.S., Collison, C., and Werz, M., 1977, Spatial memory and radial arm maze performance of rats, Learning and Motivation, 8: 289.CrossRefGoogle Scholar
  74. Otton, D.S., Walker, J.A., and Gage, F.H., 1978, Hippocampal connection and spatial discrimination, Brain Res., 139: 295.CrossRefGoogle Scholar
  75. Palm, R., and Hallmans, G., 1982, Zinc and copper metabolism in phenytoin therapy, Epilepsia, 23: 453.PubMedCrossRefGoogle Scholar
  76. Palm, R., Hallmans, G., and Sjoström, R., 1982, Zinc concentrations in normal and pathological cerebrospinal fluid, Acta Neurol, Scand., 90: 184.Google Scholar
  77. Papavasiliou, P.S., Kutt, H., Miller, S.T., Rosat, V., Wang, Y.Y., and Aronson, R.B., 1979, Seizure disorders and trace metals: manganese tissue levels in treated epileptics, Neurology, 29: 1466.CrossRefGoogle Scholar
  78. Pei, Y., Zhao, D., Huang, J., and Cao, L., 1983, Zinc-induced seizures: a new experimental model of epilepsy, Epilepsia, 24: 169.PubMedCrossRefGoogle Scholar
  79. Peters, D.P., 1978, Effects of prenatal nutritional deficiency on affiliation and aggression in rats, Phvsiol. Behay., 20: 359.CrossRefGoogle Scholar
  80. Peters, D.P., 1979, Effects of prenatal nutrition on learning and motivation in rats, Physiol. Behay., 22: 1067.CrossRefGoogle Scholar
  81. Pfeiffer, C.C., and LaMola, S., 1983, Zinc and manganese in the schizophrenia, J. Orthomolec. Psych., 12: 215.Google Scholar
  82. Pippenger, C.E., Garlock, C., Fernandez, F., Slavin, W., and Iannarone, J., 1980, Effect of antiepileptic drugs on manganese, zinc and copper concentrations in whole blood, RBC, and plasma of epileptic, in: Advances in Epileptologv: XIth Epilepsy International Symposium, R. Canger,ed., Raven Press, New York, p. 435Google Scholar
  83. Prasad, A.S., 1976, Deficiency of zinc in man and its toxicity, in: Trace Elements in Human Health and Disease, A.S. Prasad, ed., Academic Press, New York, p. 1.Google Scholar
  84. Prasad, A.S., 1979, Clinical, biochemical and pharmacological role of zinc, Ann. Rev. Pharmacol. Toxicol., 20: 393.Google Scholar
  85. Pryor, D.S., Don, N., and Macourt, D.C., 1981, Fifth day fits: a syndrome of neonatal convulsions, Arch. Dis. Childh., 56: 753.PubMedCrossRefGoogle Scholar
  86. Pulido, P., Kagi, J.H.R., and Vallee, B.L., 1966, Isolation and some properties of human metallothionein, Biochemistry, 5: 1768.PubMedCrossRefGoogle Scholar
  87. Record, I.R., Dreosti, I.E., Tulsi, R.S., Fraser, R.S., Fraser, F.J., Buckley, R.A., and Manuel, S.J., 1982, Postnatal accumulation of zinc by the rat hippocampus, Biol. Trace Element Res., 4: 279.CrossRefGoogle Scholar
  88. Rieder, H.P., Schoettli, G., and Seiler, H., 1983, Trace elements in whole blood of multiple sclerosis, Eur. Neurol., 22: 85.PubMedCrossRefGoogle Scholar
  89. Sandstead, H.H., Fosmire, G.J., Halas, E.S., Jacob, R.A., Strobel., D.S., and Marks, E.O., 1977, Zinc deficiency: effects on brain and behavior of infants, Am. J. Clin. Nutr., 31: 844.Google Scholar
  90. Sandstead, H.H., Strobel, D.A., Logan, G.M., Marks, E.O., and Jacob, R.A., 1978, Zinc deficiency in pregnant rhesus monkeys: effects on behavior of infants, Am. J. Clin, Nutr., 31: 844.PubMedGoogle Scholar
  91. Shapcott, D., Giguere, R., and Lemieux, B., 1984, Zinc and taurine in Friedreich’s ataxia, Can, J. Neurol. Sci., 11: 623.Google Scholar
  92. Sato, S.M., Frazier, J.M., and Goldberg, A.M., 1984a, The distribution and binding of zinc in the hippocampus,J. Neurosci., 4: 1662.PubMedGoogle Scholar
  93. Sato, S.M., Frazier, J.M., and Goldberg, A.M., 1984b, A kinetic study of the in vivo incorporation of Zn into the rat hippocampus, J. Neurosci., 4: 1671.PubMedGoogle Scholar
  94. Slevin, J.T., and Kasarkis, E.J., 1985, Effects of zinc on markers of glutamate and aspartate neurotransmission in rat hippocampus, Brain Res., 334: 281.PubMedCrossRefGoogle Scholar
  95. Smart, T.G., and Constanti, A., 1982, A novel effect of zinc on the lobster muscle GABA receptor, Proc. Rov. Soc. Lond., B215: 327.CrossRefGoogle Scholar
  96. Stengaard-Pedersen, K., 1982, Inhibition of enkephalin binding to opiate receptors by zinc ions: possible physiological importance in the brain, Acta Pharmacol. Toxicol., 50: 213.CrossRefGoogle Scholar
  97. Stengaard-Pedersen, K., Larson, L.-I., Fredens, K., and Rehfeld, J.F.,1984, Modulation of cholecystokinin concentrations in the rat hippocampus by chelation of heavy metals, Proc. Natl. Acad. Sci. USA, 81: 5876.PubMedCrossRefGoogle Scholar
  98. Sypert, G.W., 1982, Metallic salts and epileptogenesis, in: Physiology and Pharmacology of Epileptogenic Phenomena, M.R. Klee, H.D. Lux, and E.J. Speckman, eds., Raven Press, New York, p. 81.Google Scholar
  99. Underwood, E.J., 1977, Zinc, in: Trace Elements in Human and Animal Nutrition, E.J. Underwood, ed., Academic Press, New York, p. 196.Google Scholar
  100. Vallee, B.L., 1983, Zinc in biology and biochemistry, in: Zinc Enzymes, Vol. 5, T.G. Spiro, ed., Metal Ion in Biology Series, John Wiley and Sons, New York, p. 3.Google Scholar
  101. Webb, M., and Cain, K., 1982, Functions of metallothionein, Biochem. Pharmacol., 31: 137.PubMedCrossRefGoogle Scholar
  102. Wright, D.M., 1984, Zinc: effect and interaction with other cations in the cortex of the rat, Brain Res., 311: 343.PubMedCrossRefGoogle Scholar
  103. Wu, C.-T., Lee, J.-N., Shen, W.W., and Lee, S.-L., 1984, Serum zinc, copper, and ceruloplasmin levels in male alcoholics, Biol. Psych., 19: 1333.Google Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • M. Ebadi
    • 1
  • Y. Hama
    • 1
  1. 1.Department of PharmacologyUniversity of Nebraska College of MedicineOmahaUSA

Personalised recommendations