Pathophysiological Roles of P2 Receptors in Glial Cells

  1. Derek J. Chadwick Organizer and
  2. Jamie Goode
  1. Maria P. Abbracchio1 and
  2. Claudia Verderio1,2

Published Online: 7 OCT 2008

DOI: 10.1002/9780470032244.ch8

Purinergic Signalling in Neuron-Glia Interactions: Novartis Foundation Symposium 276

Purinergic Signalling in Neuron-Glia Interactions: Novartis Foundation Symposium 276

How to Cite

Abbracchio, M. P. and Verderio, C. (2006) Pathophysiological Roles of P2 Receptors in Glial Cells, in Purinergic Signalling in Neuron-Glia Interactions: Novartis Foundation Symposium 276 (eds D. J. Chadwick and J. Goode), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/9780470032244.ch8

Author Information

  1. 1

    Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, Milan 20133, Italy

  2. 2

    CNR Institute of Neuroscience, Cellular and Molecular Pharmacology and Department of Medical Pharmacology, Via Vanvitelli 32, 20129, Milan, Italy

Publication History

  1. Published Online: 7 OCT 2008
  2. Published Print: 21 APR 2006

Book Series:

  1. Novartis Foundation Symposia

Book Series Editors:

  1. Novartis Foundation

ISBN Information

Print ISBN: 9780470018606

Online ISBN: 9780470032244

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Keywords:

  • glial P2 receptors;
  • astroglial cell role in CNS physiopathology;
  • calcium-dependent cell–cell communication;
  • brain glial cells and functional P2 receptors;
  • ATP-mediated calcium signal in astrocytes

Summary

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.