Skip to main content
SpringerLink
Log in

Stimulated release of exogenous GABA and glutamate from cerebral cortical synaptosomes and brain slices by bis (acetato) tetrakis (imidazole) copper(II) complex

  • Original Articles
  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

In these experiments we have tested the effect of bis(acetato)tetrakis (imidazole) copper(II) on the release and uptake of 14C-GABA and 3H-glutamate from brain slices and brain cortical synaptosomes. Cu(OAc)2(Im)4 in concentrations ranging from 1 to 100 μM has increased the release of GABA and glutamate from brain slices and synaptosomal preparations in a dose-related manner when the effect on GABA release is two-fold greater than glutamate and 10-fold greater than alanine. Pretreatment with a GABA uptake inhibitor such as 1–2 mM nipecotic acid has no effect on 14C-GABA release, whereas hydroxy aspartate, the glutamate uptake inhibitor, has elevated the stimulated release of glutamate. Copper(II) chloride, the inorganic form of copper, had no significant effect either on GABA release or on glutamate release. The stimulated release of exogenous GABA and glutamate was Ca2+-dependent, because it was inhibited by EGTA, and neuronal, because it was blocked by tetrodotoxin. The recent results can explain the anticonvulsant activity of Cu(OAc)2(Im)4 against strychnine-induced seizures by increasing the net release of GABA from cortical neurons.

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. J. R. J. Sorenson, Copper chelates as possible active forms of antiarthritic agents, J. Med. Chem. 19, 135–148 (1976).

    Article  PubMed  CAS  Google Scholar 

  2. J. R. J. Sorenson, L. W. Oberley, and V. Kishore, Copper complexes: a physiological approach to the treatment of inflammatory diseases, Inorg. Chim Acta 91, 285–294 (1984).

    Article  CAS  Google Scholar 

  3. J. R. J. Sorenson, K. Ramakrishna, and T. M. Rolniak, Antiulcer activities of d-penicil lamine copper complexes, Agents Actions 12(3), 408–411 (1982).

    Article  PubMed  CAS  Google Scholar 

  4. J. R. J. Sorenson, Copper complexes offer a physiological approach to treatment of chronic diseases, Proc. Med. Chem. 26, 437–568 (1989).

    Article  CAS  Google Scholar 

  5. S. E. Gandy, M. G. Buse, J. R. J. Sorenson, et al., Attenuation of streptozotocin diabetes with superoxide dismutase like copper(II) (3,5-diisopropyl-salicylate)2 in the rat, Diabetologia 24(6), 437–440 (1993).

    Google Scholar 

  6. A.-S. Abdul-Ghani, A. L. AbuHijleh, N. Nahas, et al., Hypoglycemic effect of copper(II) acetate imidazole complexes, Biol. Trace Element Res. 54, 143–151 (1996).

    CAS  Google Scholar 

  7. J. R. J. Sorenson, Copper chelates as possible active metabolites of the antiarthritic and antiepileptic drugs, J. Appl. Nutr. 32, 4–9 (1980).

    CAS  Google Scholar 

  8. B. L. Booth, E. Pitters, B. Mayer, et al., Down regulation of porcine heart diaphorase reactivity by trimanganese hexakis (3,5-diisopropyl salicylate) Mn3(3,5-DIPS)6, and down regulation of nitric oxide synthase reactivity by Mn3(3,5-DIPS)6 and Cu(II)2(3,5-DIPS)4, Metal-Based Drugs 6, 111–120 (1999).

    Article  CAS  PubMed  Google Scholar 

  9. G. Morgant, N.-H., Dung, J.-C. Daran, et al., Low-temperature crystal structures of tetrakis-μ-3,5-diisopropylsalicylatobis-dimethyl formamido dicopper (II) and tetrakis-μ-3,5-diisopropylsalicylatobis-diethyletheratodicopper(II) and their role in modulating polymorphonuclear leukocyte activity in overcoming seizures, J. Inorg. Biochem. 81, 11–22 (2000).

    Article  PubMed  CAS  Google Scholar 

  10. J. R. J. Sorenson, L. S. F. Soderberg, L. W. Chang, et al., Copper-, iron-, manganese- and zinc-3,5-diisopropylsalicylate complexes increase survival of gamma-irradiated mice, Eur. J. Med. Chem. 38, 221–229 (1993).

    Article  Google Scholar 

  11. B. Viossat, J.-C. Duran, G. Savouret, et al., Low temperature (180 K) crystal structure, electron paramagnetic sesonance spectroscopy, and propitious anticonyulsant activities of Cu(II)2(aspirinate)4(DMF)2 and other Cu(II)2(aspirinate)4 chelates, J. Inorg. Biochem. 96, 375–385 (2003).

    Article  PubMed  CAS  Google Scholar 

  12. A.-S. Abdul-Ghani, A. Abu-Hijleh, and M. Qazzaz, The effect of bis(acetato)tetrakis(imidazole)copper(II) in delaying the onset and reducing the mortality rate of strychnine and thiosemicarbazide induced convulsions. Biol. Trace Element Res., 101, 87–95 (2004).

    Article  CAS  Google Scholar 

  13. P. Y. Boukan, E. A. Busnot, F. Busnot, et al., Structure du di-μ-acetato-bis[acetato bis(methyl-1 imidazol) cuivre(II)]hexahydrate, Acta Crystallogr. B38, 2458–2461 (1982).

    Google Scholar 

  14. P. Lemoine, B. Viossat, G. Morgant, et al., Synthesis, crystal structure, EPR properties and anticonvulsant activities of binuclear and mononuclear 1,10-phenanthroline and salicylate ternary copper(II) complexes, J. Inorg. Biochem. 89, 18–28 (2002).

    Article  PubMed  CAS  Google Scholar 

  15. A. L. AbuHijleh, C. Wood, and I. Y. Ahmed, Synthesis and molecular structure of monomeric copper(II) acetate with 2-methylimidazole and 1,2-dimethylimidazole, Inorg. Chim. Acta 190, 11–17 (1991).

    Article  CAS  Google Scholar 

  16. A. L. AbuHijleh and C. Woods, Synthesis, spectroscopic and structural characterization of bis(acetato)tetrakis(imidazole) copper(II): a model complex of DNA binding, Inorg. Chim. Acta 194, 9–14 (1992).

    Article  CAS  Google Scholar 

  17. E. G. Gray and W. P. Whittaker, The isolation of nerve ending from brain; an electron-microscopic study of cell fragments derived by homogenization and centrifugation, J. Anat. 96, 79–88 (1962).

    PubMed  CAS  Google Scholar 

  18. H. F. Bradford, G. W. Bennett, and A. J. Thomas, Depolarizing stimuli and the release of physiologically active amino acids from suspensions of mammalian synaptosomes, J. Neurochem. 21, 495–505 (1973).

    Article  PubMed  CAS  Google Scholar 

  19. J. R. J. Sorenson, D. O. Rauls, K. Ramakrishna, et al., in Trace Substances in Environmental Health—XIII. Anticonvulsant Activity of Some Copper Complexes, D. D. Hemphill (ed.), University of Missouri Press, Columbia, MO, pp. 360–367 (1979).

    Google Scholar 

  20. H. H. A. Dollwet, J. B. McNicholas, A. Pezesk, et al., Superoxide dismutase-mimetic activity of antiepileptic drug copper complexes, Trace Elements Med. 4, 13–20 (1987).

    CAS  Google Scholar 

  21. G. Morgant, N.-H. Dung, J.-C. Daran, et al., Low-temperature crystal structures of tetrakis-μ-3,5-diisopropylsalicylatobis-dimethyl formamido dicopper (II) and tetrakis-μ-3,5-diisopropylsalicylatobis-diethyletheratodicopper(II) and their role in modulating polymorphonuclear leukocyte activity in overcoming seizures, J. Inorg. Biochem. 81, 11–22 (2000).

    Article  PubMed  CAS  Google Scholar 

  22. H. F. Bradford, in Biochemistry and Neurology, H. F. Bradford and C. D. Marsden, eds., Academic, London, pp. 195–212 (1976).

    Google Scholar 

  23. S. Simler, L. Ciesiclski, M. Maitre, et al., Effect of sodium n-dipropyl acetate on audiogenic seizures and brain γ-amino butyric acid levels, Biochem. Pharmacol. 22, 1701 (1973).

    Article  PubMed  CAS  Google Scholar 

  24. R. M. Pinder, R. N. Brogden, T. M. Speight, et al., Viloxazine: a review of its pharmacological properties and therapeutic efficacy in depressive illness, Drugs 13(6), 401–421 (1977).

    PubMed  CAS  Google Scholar 

  25. B. S. Meldrum, Epilepsy and gamma-amino butyric acid-mediated inhibition, Int. Rev. Neurobiol. 17, 1–36 (1975).

    Article  PubMed  CAS  Google Scholar 

  26. A.-S. Abdul-Ghani, J. Coutinho-Neto, D. Druce, et al., Effects of anti-convulsants on the in vivo and in vitro release of GABA, Biochem. Pharmacol. 30, 363–368 (1981).

    Article  PubMed  CAS  Google Scholar 

  27. A.-S. Abdul-Ghani, P. J. Norris, C. C. T. Smith, et al., Effect of μ-acetylenic GABA and γ-vinyl GABA on synaptosomal release and uptake of GABA, Biochem. Pharmacol. 30(11), 1203–1209 (1981).

    Article  PubMed  CAS  Google Scholar 

  28. O. D. Dolly, C. K. Tse, J. W. Spokes, and C. R. Diniz. Effect of β-bangarotoxin and Tityus-toxin on uptake and release of neurotransmitters, Biochem. Soc. Trans. 6, 652–654 (1978).

    PubMed  CAS  Google Scholar 

  29. J. Coutinho-Neto, A.-S. Abdul-Ghani, P. J. Norris, et al., The effect of Scorpiom venom toxin on the release of amino acid neurotransmitters from cerebral cortex in vivo and in vitro, J. Neurochem. 35(3), 558–565 (1980).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Physiology Department, Faculty of Medicine, Al-Quds University, P. O. Box 19356, Jerusalem, West Bank, Palestine

    Abdul-Salam Abdul-Ghani

  2. Department of Chemistry, Birzeit University, P. O. Box 14, Birzeit, West Bank, Palestine

    Abdul-Latif Abu-Hijleh

  3. Department of Biology and Biochemistry, Faculty of Science, Birzeit University, P. O. Box 14, Birzeit, West Bank, Palestine

    Munir Qazzaz, Ashraf Muhaisen & Rula Abdul Ghani

Authors
  1. Abdul-Salam Abdul-Ghani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Abdul-Latif Abu-Hijleh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Munir Qazzaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ashraf Muhaisen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rula Abdul Ghani
    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

Abdul-Ghani, AS., Abu-Hijleh, AL., Qazzaz, M. et al. Stimulated release of exogenous GABA and glutamate from cerebral cortical synaptosomes and brain slices by bis (acetato) tetrakis (imidazole) copper(II) complex. Biol Trace Elem Res 108, 205–214 (2005). https://doi.org/10.1385/BTER:108:1-3:205

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1385/BTER:108:1-3:205

Index Entries

Search

Navigation