Antagonists of P2 receptor prevent NGF-dependent neuritogenesis in PC12 cells

Nadia D'Ambrosi, Fabio Cavaliere, Daniela Merlo, Luisa Milazzo, Delio Mercanti, Cinzia Volonté

Research output: Contribution to journalArticlepeer-review


The pheochromocytoma PC12 cell line that develops neuronal characteristics of sympathetic cells after treatment with nerve growth factor (NGF) represents a well-established cellular model system for studying NGF signalling. Interesting information on the different mechanistic pathways of NGF can be obtained by adopting the pharmacological approach of inhibiting P2 receptors, expressed in naive PC12 cells and recognised as important biological mediators of neurotransmitters and growth factors. We show here that Basilen Blue, an antagonist of P2 receptor, reversibly prevents NGF- dependent neurite outgrowth with an IC50 in the 5-10 μM range. Suramin, oxidised-ATP and diisothiocyanatostilbene-disulfonic acid, differently from other purinoceptor ligands, are also effective in this regard. NGF-dependent regeneration and stability of neurites, selected NGF-dependent extracellular and intracellular protein phosphorylations, binding of [3H] ATP to PC12 cell membranes are also modulated by Basilen Blue. On the contrary, cell adhesion, cellular duplication, 5'-nucleotidase activity, NGF-induced tyrosine autophosphorylation of TrkA receptors are not affected. NGF furthermore directly modulates the extracellular release of ATP and especially the levels of P2X2 receptor protein in PC12 cells. In addition, extracellular ATP improves the neuritogenic effect of sub-optimal concentrations of NGF. Our study identifies P2 receptor ligands, particularly Basilen Blue, as useful tools to dissect different NGF-evoked functions, suggesting a mechanistic role for P2 receptors in the signalling pathways of NGF. (C) 2000 Elsevier Science Ltd.

Original languageEnglish
Pages (from-to)1083-1094
Number of pages12
Issue number6
Publication statusPublished - May 2000


  • 5'- nucleotidase
  • ATP binding
  • Basilen Blue
  • Intracellular-extracellular phosphorylations
  • Neuronal differentiation
  • P2X receptor
  • Trk

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology


Dive into the research topics of 'Antagonists of P2 receptor prevent NGF-dependent neuritogenesis in PC12 cells'. Together they form a unique fingerprint.

Cite this