Skip to main content
SpringerLink
Log in

The Effect of Endogenous Modulator Endobain E on NMDA Receptor Is Interfered by Zn22+ but Is Independent of Modulation by Spermidine

  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

A brain endogenous factor, termed endobain E, allosterically decreases [3H]dizocilpine binding to NMDA receptor. Such effect depends on receptor activation by the coagonists glutamate and glycine and is interfered by channel blockers, suggesting its interaction with the inner surface of the associated channel. To further analyze endobain E effect on NMDA receptor, in the current study competitive [3H]dizocilpine binding assays to brain membranes were performed with Zn2+ to block the associated channel, as well as with spermidine (SPD), which exerts positive allosteric modulation of NMDA receptor. Partially or nonadditive effects on [3H]dizocilpine binding were recorded, respectively, in the presence of endobain E at a concentration that inhibits binding 25% plus IC25 Zn2+ or endobain E at a concentration that inhibits binding 50% plus IC50 Zn2+. With an endobain E concentration that decreases 25% ligand binding, SPD potentiated binding over a wide concentration range but failed to modify endobain E effect. Similarly, [3H]dizocilpine binding reduction over a wide endobain E concentration range remained unaltered by high SPD concentrations. Additive effects were observed with endobain E at a concentration that decreases binding 25% plus IC25 SPD site antagonists arcaine or ifenprodil. Zn2+ experiments indicated that endobain E effect is interfered by channel blockade produced by this ion. Although endobain E effect is dependent on NMDA receptor activation by glutamate and glycine, it proves independent of the positive modulation exerted by SPD. Thus the endogenous modulator seems not to interact at NMDA receptor polyamine site, favoring the hypothesis that endobain E binds inside the associated channel.

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. Dingledine, R., and McBain, C. J. 1999. Glutamate and aspartate. Pages 315–333, in Siegel, G. J., Agranoff, B. W., Albers, R. W., Fisher, S. K., and Uhler, M. D. (eds.), Basic Neurochemistry, 6th ed., Lippincott-Raven Press, Philadelphia.

    Google Scholar 

  2. Dingledine, R., Borges, K., Bowie, D., and Traynelis, S. F. 1999. The glutamate receptor ion channels. Pharmacol. Rev. 51:7–61.

    Google Scholar 

  3. Mothet, J. P., Parent, A. T., Wolosker, H., Brady, R. O. Jr., Linden, D. J., Ferris, C. D., Rogawski, M. A., and Snyder, S. H. 2000. D-Serine is an endogenous ligand for the glycine site of the N-methyl-D-aspartate receptor. Proc. Natl. Acad. Sci. USA 97:4926–4931.

    Google Scholar 

  4. Stone, T. W., and Addae, J. I. 2002. The pharmacological manipulation of glutamate receptors and neuroprotection. Eur. J. Pharmacol. 447:285–296.

    Google Scholar 

  5. Trombley, P. Q., and Shepherd, G. M. 1996. Differential modulation by zinc and copper of amino acid receptors from rat olfactory bulb neurons. J. Neurophysiol. 76:2536–2546.

    Google Scholar 

  6. Fayyazuddin, A., Villarroel, A., Le Goff, A., Lerma, J., and Neyton, J. 2000. Four residues of extracellular N-terminal domain of the NR2A subunit control high-affinity Zn2+ binding to NMDA receptors. Neuron 25:683–694.

    Google Scholar 

  7. Rodríguez de Lores Arnaiz, G., Reinés, A., Herbin, T., and Peña, C. 1998. Na+, K+-ATPase interaction with a brain endogenous inhibitor (endobain E). Neurochem. Int. 33:425–433.

    Google Scholar 

  8. Vatta, M., Peña, C., Fernández, B., and Rodríguez de Lores Arnaiz, G. 1999. A brain Na+,K+-ATPase inhibitor (endobain E) enhances norepinephrine release in rat hypothalamus. Neuroscience 90:573–579.

    Google Scholar 

  9. Rodríguez de Lores Arnaiz, G., and Peña, C. 1995. Characterization of synaptosomal membrane Na+,K+-ATPase inhibitors. Neurochem. Int. 27:319–327.

    Google Scholar 

  10. Rodríguez de Lores Arnaiz, G., Herbin, T., and Peña, C. 2003. A comparative study between a brain Na+,K+-ATPase inhibitor (endobain E) and ascorbic acid. Neurochem. Res. 28:903–910.

    Google Scholar 

  11. Reinés, A., Peña, C., and Rodríguez de Lores Arnaiz, G. 2001. [3H]Dizocilpine binding to N-methyl-D-aspartate (NMDA) receptor is modulated by an endogenous Na+,K+-ATPase inhibitor: Comparison with ouabain. Neurochem. Int. 39:301–310.

    Google Scholar 

  12. Reinés, A., Peña, C., and Rodríguez de Lores Arnaiz, G. 2001. NMDA receptor activation favours its allosteric modulation by an endogenous Na+,K+-ATPase inhibitor. J. Neurochem. 78:(Suppl. 1) BP18–BP44. (Abstract).

    Google Scholar 

  13. Ogita, K., and Yoneda, Y. 1999. Signal transduction through ion channels associated with excitatory amino acid receptors. Methods Enzymol. 294:385–410.

    Google Scholar 

  14. Yoneda, Y., Ogita, K., and Enomoto, R. 1991. Characterization of spermidine-dependent [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) binding in brain synaptic membranes treated with Triton X-100. J. Pharmacol. Exp. Ther. 256:1161–1172.

    Google Scholar 

  15. Rodríguez de Lores Arnaiz, G., and Antonelli de Gómez de Lima, M., 1986. Partial characterization of an endogenous factor which modulates the effect of catecholamines on synaptosomal Na+,K+-ATPase. Neurochem. Res. 11:933–947.

    Google Scholar 

  16. Cowburn, R. F., Wiehager, B., Trief, E., Li-Li, M., and Sundström, E. 1997. Effects of β-amyloid-(25-35) peptide on radioligand binding to excitatory amino acid receptor and voltage-dependent calcium channels: Evidence for a selective affinity for the glutamate and glycine recognition sites of NMDA receptor. Neurochem. Res. 22:1437–1442.

    Google Scholar 

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

    Google Scholar 

  18. Christine, C. W., and Choi, D. W. 1990. Effect of Zinc on NMDA receptor-mediated channel currents in cortical neurons. J. Neurosci. 10:108–116.

    Google Scholar 

  19. Ransom, R. W., and Stec, N. L. 1988. Cooperative modulation of [3H]MK-801 binding to the N-methyl-D-aspartate receptor-ion channel complex by L-glutamate, glycine, and polyamines. J. Neurochem. 51:830–836.

    Google Scholar 

  20. Reynolds, I. J., and Miller, R. J. 1989. Ifenprodil is a novel type of N-methyl-D-aspartate receptor antagonist: Interaction with polyamines. Mol. Pharmacol. 36:758–765.

    Google Scholar 

  21. Reynolds, I. J. 1990. Arcaine uncovers dual interaction of polyamines with the N-methyl-D-aspartate receptor. J. Pharmacol. Exp. Ther. 255:1001–1007.

    Google Scholar 

  22. Sacaan, A. I., and Johnson, K. M. 1990. Competitive inhibition of magnesium induced [3H]N-(1-[thienyl]cyclohexyl)piperidine binding by arcaine: Evidence for a shared spermidine-magnesium binding site. Mol. Pharmacol. 38:705–710.

    Google Scholar 

  23. Donevan, S. D., Jones, S. M., and Rogawski, M. A. 1992. Arcaine blocks N-methyl-D-aspartate receptor responses by an open channel mechanism: Whole-cell and single-channel recording studies in cultured hippocampal neurons. Mol. Pharmacol. 41:727–735.

    Google Scholar 

  24. Rock, D. M., and MacDonald, R. L. 1992. Spermine and related polyamines produce a voltage-dependent reduction of N-methyl-D-aspartate receptor single-channel conductance. Mol. Pharmacol. 42:157–164.

    Google Scholar 

  25. Reynolds, I. J. 1992. 1,5-(Diethylamino)piperidine, a novel spermidine analogue that more specifically activates the N-methyl-D-aspartate receptor-associated polyamine site. Mol. Pharmacol. 41:989–992.

    Google Scholar 

  26. Bonhaus, D. W., and McNamara, J. O. 1988. N-methyl-D-aspartate receptor regulation of uncompetitive antagonist binding in rat brain membranes: Kinetic analysis. Mol. Pharmacol. 34:250–255.

    Google Scholar 

  27. Kloog, Y., Haring, R., and Sokolovsky, M. 1988. Kinetic characterization of the phencyclidine-N-methyl-D-aspartate receptor interaction: Evidence for a steric blockade of the channel. Biochemistry 27:843–848.

    Google Scholar 

  28. Reynolds, I. J., and Miller, R. J. 1988. Multiple sites for the regulation of the N-methyl-D-aspartate receptor. Mol. Pharmacol. 33:581–584.

    Google Scholar 

  29. Yoneda, Y., Ogita, K., Kouda, T., and Ogawa, Y. 1990. Radioligand labeling of N-methyl-D-aspartic acid (NMDA) receptors by [3H]( ± )-3-(2-carboxypiperazin-4-yl)phosphonic acid in brain synaptic membrane treated with Triton X-100. Biochem. Pharmacol. 39:225–228.

    Google Scholar 

  30. Williams, K., Dawson, V. L., Romano, C., Dichter, M. A., and Molinoff, P. B. 1990. Characterization of polyamines having agonist, antagonist and inverse agonist effect at the polyamine recognition site of the NMDA receptor. Neuron 5:199–208.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Instituto de Biología Celular y Neurociencias, “Prof. E. De Robertis,” Facultad de Medicina. Cátedra de Farmacología, Universidad de Buenos Aires, Buenos Aires, Argentina

    A. Reinés, S. Zárate & G. Rodríguez de Lores Arnaiz

  2. IQUIFIB-CONICET, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina

    C. Peña

Authors
  1. A. Reinés
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Zárate
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Peña
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. Rodríguez de Lores Arnaiz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G. Rodríguez de Lores Arnaiz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reinés, A., Zárate, S., Peña, C. et al. The Effect of Endogenous Modulator Endobain E on NMDA Receptor Is Interfered by Zn22+ but Is Independent of Modulation by Spermidine. Neurochem Res 29, 819–825 (2004). https://doi.org/10.1023/B:NERE.0000018856.99773.71

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:NERE.0000018856.99773.71

Search

Navigation