Pathophysiological Roles of P2 Receptors in Glial Cells

Maria P. Abbracchio, Claudia Verderio

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Extracellular nucleotides act through specific receptors on target cells: the seven ionotropic P2X and the eight G protein-coupled P2Y receptors. All these receptors are expressed by brain astroglia and microglia. In astrocytes, P2 receptors have been implicated in short-term calcium-dependent cell-cell communication. Upon mechanical stimulation or activation by other transmitters, astrocytes release ATP and respond to ATP with a propagating wave of intracellular calcium increases, allowing a homotypic astrocyte-astrocyte communication, as well as an heterotypic signalling which also involves neurons, oligodendrocytes and microglia. Astrocytic P2 receptors also mediate reactive astrogliosis, a reaction contributing to neuronal death in neurodegenerative diseases. Signalling leading to inflammatory astrogliosis involves induction of cyclo-oxygenase 2 through stimulation of ERK1,2 and of the transcriptional factors AP-1 and NF-κB. Microglia also express several P2 receptors linked to intracellular calcium increases. P2 receptor subtypes are differentially regulated by typical proinflammatory signals for these cells (e.g. lipopolysaccharide), suggesting specific roles in brain immune responses. Globally, these findings highlight the roles of P2 receptors in glial cell pathophysiology suggesting a contribution to neurodegenerative diseases characterized by excessive gliosis and neuro-inflammation. They also open up the possibility of modulating brain damage by ligands selectively targeting the specific P2 receptor subtypes involved in the gliotic response.

Original languageEnglish
Title of host publicationPurinergic Signalling in Neuron-Glia Interactions
PublisherWiley Blackwell
Pages91-103
Number of pages13
ISBN (Print)9780470032244, 0470018607, 9780470018606
DOIs
Publication statusPublished - Oct 7 2008

Keywords

  • Astroglial cell role in CNS physiopathology
  • ATP-mediated calcium signal in astrocytes
  • Brain glial cells and functional P2 receptors
  • Calcium-dependent cell-cell communication
  • Glial P2 receptors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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