Archives of Toxicology

, Volume 64, Issue 2, pp 161–164 | Cite as

A mechanism of cadmium poisoning: The cross effect of calcium and cadmium in the calmodulin-dependent system

  • Den'etsu Sutoo
  • Kayo Akiyama
  • Shunichiro Imamiya
Short Communication

Abstract

The effects of the intraventricular (IVT) administration of cadmium on the amount of dopamine (DA) in various regions of the mice brain were analyzed immunohistochemically using a microphotometry system. DA levels in the neostriatum and nucleus accumbens were increased by approximately 30% (p<0.01) by the IVT administration of CdCl2 (1 μmol/kg). This effect was abolished by the calmodulin antagonist, W-7 (4.2 μg/mouse, IVT). The effects of cadmium on DA levels in the brain were very similar to those seen with calcium. Combining these results with our previous finding that calmodulin does not have the ability to distinguish between calcium and cadmium, a mechanism of cadmium poisoning is suggested in which cadmium activates catecholamine synthesizing enzyme and numerous other enzymes through calmodulin-dependent systems, thereby disturbing many functions in the organism.

Key words

Cadmium Calmodulin Dopamine Neostriatum Nucleus accumbens 

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References

  1. Akiyama K, Sutoo D (1988a)1H-NMR studies of calmodulin: the modifying effect of W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide) on the calcium-induced conformational changes of calmodulin. Jpn J Pharmacol 48: 157–164PubMedGoogle Scholar
  2. Akiyama K, Sutoo D (1988b) The effects of cadmium on the immunohistochemical distribution of brain biogenic amines and chemical structure of brain calmodulin. Jpn J Psychopharmacol 8: 175–176Google Scholar
  3. Arranz MA, Perez MI, Saiz-Vadillo MC, Basagoiti I, Katarneh SM, Ribas B, Cadorniga R (1984) Pharmacokinetics of cadmium-109 in blood and cerebral structures of the rat. Rev Esp Fisiol 40: 365–370PubMedGoogle Scholar
  4. Biber A, Schmid G, Hempel K (1984) Calmodulin content in specific brain areas. Exp Brain Res 56: 323–326CrossRefPubMedGoogle Scholar
  5. Clark WG, Vivonia CA, Baxter CF (1968) Accurate freehand injection into the lateral brain ventricle of the conscious mouse. J Appl Physiol 25: 319–321PubMedGoogle Scholar
  6. Egrie JC, Campbell JA, Flangas AL, Siegel FL (1977) Regional, cellular and subcellular distribution of calcium-activated cyclic nucleotide phosphodiesterase and calcium-dependent regulator in porcine brain. J Neurochem 28: 1207–1213PubMedGoogle Scholar
  7. Geffard M, Buijs RM, Seguela P, Pool CW, Le Moal M (1984) First demonstration of highly specific and sensitive antibodies against dopamine. Brain Res 294: 161–165CrossRefPubMedGoogle Scholar
  8. Kakiuchi S, Yasuda S, Yamazaki R, Teshima Y, Kanda K, Kakiuchi R, Sobue K (1982) Quantitative determinations of calmodulin in the supernatant and particulate fractions of mammalian tissues. J Biochem (Tokyo) 92: 1041–1048Google Scholar
  9. Klee CB, Vanaman TC (1982) Calmodulin. In: Anfinsen CB, Edsall JT, Richards FM (eds) Advances in protein chemistry, vol 35. Academic Press, New York, pp 213–321Google Scholar
  10. Kluver H, Barrera E (1953) A method for the combined staining of cells and fibers in the nervous system. J Neuropathol Exp Neurol 12: 400–404PubMedGoogle Scholar
  11. König JFR, Klippel RA (1963) The rat brain: a stereotaxic atlas of the forebrain and lower parts of the brain stem. Williams and Wilkins, BaltimoreGoogle Scholar
  12. Martin SR, Bayley PM (1986) The effects of calcium and cadmium on the secondary and tertiary structure of bovine testis calmodulin. A circular-dichroism study. Biochem J 238: 485–490PubMedGoogle Scholar
  13. McRae-Degueurce A, Geffard M (1986) One perfusion mixture for immunocytochemical detection of noradrenaline, dopamine, serotonin and acetylcholine in the same rat brain. Brain Res 376: 217–219CrossRefPubMedGoogle Scholar
  14. Niewenhuis RJ, Prozialeck WC (1987) Calmodulin inhibitors protect against cadmium-induced testicular damage in mice. Biol Reprod 37: 127–133PubMedGoogle Scholar
  15. O'Callaghan JP, Miller DB (1986) Diethyldithiocarbamate increases distribution of cadmium to brain but prevents cadmium-induced neurotoxicity. Brain Res 370: 354–358CrossRefPubMedGoogle Scholar
  16. Pellegrino LJ, Pellegrino AS, Cushman AJ (1979) A stereotaxic atlas of the rat brain. Plenum Press, New YorkGoogle Scholar
  17. Perrino BA, Chou IN (1986) Role of calmodulin in cadmium-induced microtubule disassembly. Cell Biol Int Rep 10: 565–573CrossRefPubMedGoogle Scholar
  18. Saavedra JM, Zivin J (1976) Tyrosine hydroxylase and dopamineβ-hydroxylase: distribution in discrete areas of the rat limbic system. Brain Res 105: 517–524CrossRefPubMedGoogle Scholar
  19. Sutoo D, Akiyama K, Iimura K (1985) Effect of calmodulin antagonists on calcium and ethanol-induced sleeping time in mice. Pharmacol Biochem Behav 23: 627–631CrossRefPubMedGoogle Scholar
  20. Sutoo D, Akiyama K, Iimura K (1986a) The ability of divalent cations to enhance ethanol-induced sleeping time. Alcohol 3: 69–72CrossRefPubMedGoogle Scholar
  21. Sutoo D, Akiyama K, Fujii N, Matsushita K (1986b) Divalent cation dependent conformations of brain calmodulin detected by1HNMR. Jpn J Pharmacol 40: 169–173PubMedGoogle Scholar
  22. Sutoo D, Akiyama K, Fujii N, Matsushita K (1986c)1H-NMR studies of calmodulin: the effect of W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide) and Ca2+ on conformational changes of calmodulin. Biochim Biophys Acta 873: 156–160PubMedGoogle Scholar
  23. Sutoo D, Akiyama K, Maeda I (1987) The effect of cadmium administration on the biogenic amine distributions and amounts in the mouse brain. Kitasoto Arch Exp Med 60: 157–166Google Scholar
  24. Sutoo D, Akiyama K, Fujii N, Matsushita K (1988a)1H-NMR studies of calmodulin: various divalent cation-induced conformational changes. Kitasato Arch Exp Med 61: 149–160PubMedGoogle Scholar
  25. Sutoo D, Akiyama K, Maeda I (1988b) The development of a high sensitivity and high linearity fluorescence microphotometry system for distribution analysis of neurotransmitter in the brain. Folia Pharmacol Jpn 91: 173–180Google Scholar
  26. Sutoo D, Akiyama K, Geffard M (1989a) Central dopamine-synthesis regulation by the calcium-calmodulin dependent system. Brain Res Bull 22: 565–569CrossRefPubMedGoogle Scholar
  27. Sutoo D, Akiyama K, Fujii N, Matsushita K (1989b)1H-NMR studies of calmodulin: the character of the calcium binding sites. Jpn J Pharmacol 50: 217–227PubMedGoogle Scholar
  28. Suzuki Y, Chao SH, Zysk JR, Cheung WY (1985) Stimulation of calmodulin by cadmium ion. Arch Toxicol 57: 205–211CrossRefPubMedGoogle Scholar
  29. Wang Z, Hu H (1984) Effects of methyl mercury on brain biogenic amines in the rat. Beijing Yixueyuan Xuebao 16: 245–247Google Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • Den'etsu Sutoo
    • 1
  • Kayo Akiyama
    • 1
  • Shunichiro Imamiya
    • 2
  1. 1.Institute of Medical ScienceUniversity of TsukubaIbarakiJapan
  2. 2.School of Hygienic SciencesKitasato UniversityKanagawaJapan

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