Neuroprotective effects of modulators of P2 receptors in primary culture of CNS neurones

C. Volonté, M. T. Ciotti, N. D'Ambrosi, B. Lockhart, M. Spedding

Research output: Contribution to journalArticle

Abstract

In previous studies (Volonte and Merlo, 1996. J. Neurosci. Res. 45, 183-193) basilen blue was shown to be a P2 receptor antagonist which abrogated glutamate-mediated cytotoxicity in cerebellar neurones in primary culture. Our work has now been extended to evaluate the neuroprotective action of the compound in additional neuronal systems, as well as in a different paradigm of cell death. We show that basilen blue prevents L-glutamate-mediated neurotoxicity in rat cerebellar (90-100% inhibition), cortical (60-70%) and hippocampal (50%) neurones. Similarly, glutamate-dependent progressive darkening of cell bodies, loss of phase-brightness and rapid cellular swelling are inhibited. Basilen blue is significantly less toxic and more effective at blocking L-glutamate toxicity in mixed cortical/glial cultures, compared to its structural analogue cibacron blue. Moreover, its neuroprotective effect is correlated with the time of incubation with granule neurones. Other purinoceptor ligands, including 2,2'-pyridylisatogen, but not pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid 4-sodium, are also effective in preventing glutamate toxicity. Furthermore, basilen blue prevents serum deprivation- and low potassium-induced apoptotic cell death in cerebellar granule neurones. In summary, our data extend and reinforce the possibility of a potential therapeutic use of P2 receptor modulators as neuroprotective agents for the central nervous system. Copyright (C) 1999 Elsevier Science Ltd.

Original languageEnglish
Pages (from-to)1335-1342
Number of pages8
JournalNeuropharmacology
Volume38
Issue number9
DOIs
Publication statusPublished - Sep 1999

Keywords

  • Basilen blue
  • Excitotoxicity
  • Neuroprotection
  • Purinoceptors
  • Pyridylisatogen

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

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    Volonté, C., Ciotti, M. T., D'Ambrosi, N., Lockhart, B., & Spedding, M. (1999). Neuroprotective effects of modulators of P2 receptors in primary culture of CNS neurones. Neuropharmacology, 38(9), 1335-1342. https://doi.org/10.1016/S0028-3908(99)00034-9