Acta Biologica Hungarica

, Volume 56, Issue 3–4, pp 177–183 | Cite as

L-Glutamate and Phorbol Ester Stimulate The Release of Secretory Amyloid Precursor Protein from Rat Cortical Synaptosomes

  • L. KirazovEmail author
  • E. Kirazov
  • R. Schliebs


Treatment of rat cortical synaptosomes with micromolar concentrations of L-glutamate stimulated the release of the secreted form of amyloid precursor protein in a concentration-dependent, however biphasic manner as assayed by semiquantitative Western blot analysis. The secreted amyloid precursor protein released from synaptosomes into the incubation medium was highest in the presence of 500 μM L-glutamate (about 64% over the level assayed in the incubation medium in the absence of any drug). In contrast, direct stimulation of protein kinase C by phorbol-12-myristate-13-acetate resulted in a concentration- independent increase in secretory amyloid precursor protein release by about 100% already detectable at a concentration of 0.1 μM but with no significant change at higher concentrations up to 10 μM. The presented data show that there is a constitutive release of secretory amyloid precursor protein from synaptosomes and suggest that (i) processing of amyloid precursor protein at the synaptic level is controlled by L-glutamate presumably via activation of protein kinase C, and (ii) isolated cortical synaptosomes represent a useful experimental approach to selectively study amyloid precursor protein metabolism at the synaptic level.


Secreted amyloid precursor protein synaptosomes glutamate phorbol ester protein kinase C 


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  1. 1.
    Bayer, T. A., Wirths, O., Majtenyi, K., Hartmann, T., Multhaupt, G., Beyreuther, K., Czech, C. (2001) Key factors in Alzheimer’s disease: β-amyloid precursor protein processing, metabolism and intraneuronal transport. Brain Pathol. 11, 1–11.CrossRefGoogle Scholar
  2. 2.
    Esch, F. S., Keim, P. S., Beattie, E. C., Blacher, R. W., Culwell, A. R., Oltersdorf, T., McClure, D., Ward, P. J. (1990) Cleavage of amyloid beta peptide during constitutive processing of its precursor. Science 248, 1122–1124.CrossRefGoogle Scholar
  3. 3.
    Evin, G., Weidemann, A. (2002) Biogenesis and metabolism of Alzheimer’s disease amyloid peptide. Peptides 23, 1285–1297.CrossRefGoogle Scholar
  4. 4.
    Harrison, S. M., Jarvie, P. E., Dunkley, P. R. (1988) A rapid Percoll gradient procedure for isolation of synaptosomes directly from an S1 fraction: viability of subcellular fractions. Brain Res. 441, 72–80.CrossRefGoogle Scholar
  5. 5.
    Kirazov, L., Venkov, L., Kirazov, E. (1993) A comparison of the Lowry and the Bradford protein assays as applied for protein estimation of membrane-containing fractions. Analyt. Biochem. 208, 44–48.CrossRefGoogle Scholar
  6. 6.
    Kirazov, L., Löffler, T., Schliebs, R., Bigl, V. (1997) Glutamate-stimulated release of secretory amyloid precursor proteins from cortical rat brain slices. Neurochem. Int. 30, 557–563.CrossRefGoogle Scholar
  7. 7.
    Lee, R. K. K., Wurtman, R. J., Cox, A. J., Nitsch, R. M. (1995) Amyloid precursor protein processing is stimulated by metabotropic glutamate receptors. Proc. Natl. Acad. Sci. U.S.A. 92, 8083–8087.CrossRefGoogle Scholar
  8. 8.
    Mills, J., Reiner, P. B. (1999) Regulation of amyloid precursor protein cleavage. J. Neurochem. 72, 443–460.CrossRefGoogle Scholar
  9. 9.
    Moya, K. L., Benowitz, L. I., Schneider, G. E., Allinquant, B. (1994) The amyloid precursor protein is developmentally regulated and correlated with synaptogenesis. Devl. Biol. 161, 597–603.CrossRefGoogle Scholar
  10. 10.
    Nitsch, R. M., Slack, B. E., Wurtman, R. J., Growdon, J. H. (1992) Release of Alzheimer’s amyloid precursor derivatives stimulated by activation of muscarinic acetylcholine receptors. Science 258, 304–307.CrossRefGoogle Scholar
  11. 11.
    Nitsch, R. M., Deng, M. H., Growdon, J. H., Wurtman, R. J. (1996) Serotonin 5-HT2a and 5-HTc receptors stimulate amyloid precursor protein ectodomein secretion. J. Biol. Chem. 271, 4188–4194.CrossRefGoogle Scholar
  12. 12.
    Rossner, S., Ueberham, U., Yu, J., Kirazov, L., Schliebs, R., Regino-Perez- Polo, J., Bigl, V. (1997) In vivo regulation of amyloid precursor protein secretion by cholinergic activity. Eur. J. Neurosci. 9, 2125–2134.CrossRefGoogle Scholar
  13. 13.
    Ulus, I. H., Wurtman, R. J. (1997) Metabotropic glutamate receptor agonists increase release of soluble amyloid precursor protein derivatives from rat brain cortical and hippocampal slices. J. Pharmacol. Exp. Therapeut. 281, 149–154.Google Scholar
  14. 14.
    Vickers, J. C., Dickson, T. C., Adlard, P. A., Saunders, H. L., King, C. E., McCormack, G. (2001) The cause of neuronal degeneration in Alzheimer’s disease. Progress Neurobiol. 60, 139–165.CrossRefGoogle Scholar

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© Akadémiai Kiadó, Budapest 2005

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Authors and Affiliations

  1. 1.Department of Neuromorphology, Institute of Experimental Morphology and AnthropologyBulgarian Academy of SciencesSofiaBulgaria
  2. 2.Department of NeurochemistryPaul Flechsig Institute for Brain ResearchLeipzigGermany

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