Pathophysiological roles of P2 receptors in glial cells

Maria P. Abbracchio, Claudia Verderio

Research output: Chapter in Book/Report/Conference proceedingConference contribution

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 publicationNovartis Foundation Symposium
Pages91-103
Number of pages13
Volume276
Publication statusPublished - 2006

Publication series

NameNovartis Foundation Symposium
Volume276
ISSN (Print)15282511

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Neuroglia
Astrocytes
Microglia
Neurodegenerative Diseases
Brain
Adenosine Triphosphate
Calcium
Gliosis
Calcium Signaling
Oligodendroglia
Transcription Factor AP-1
Prostaglandin-Endoperoxide Synthases
G-Protein-Coupled Receptors
Cell Communication
Lipopolysaccharides
Nucleotides
Ligands
Inflammation
Neurons

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Abbracchio, M. P., & Verderio, C. (2006). Pathophysiological roles of P2 receptors in glial cells. In Novartis Foundation Symposium (Vol. 276, pp. 91-103). (Novartis Foundation Symposium; Vol. 276).

Pathophysiological roles of P2 receptors in glial cells. / Abbracchio, Maria P.; Verderio, Claudia.

Novartis Foundation Symposium. Vol. 276 2006. p. 91-103 (Novartis Foundation Symposium; Vol. 276).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abbracchio, MP & Verderio, C 2006, Pathophysiological roles of P2 receptors in glial cells. in Novartis Foundation Symposium. vol. 276, Novartis Foundation Symposium, vol. 276, pp. 91-103.
Abbracchio MP, Verderio C. Pathophysiological roles of P2 receptors in glial cells. In Novartis Foundation Symposium. Vol. 276. 2006. p. 91-103. (Novartis Foundation Symposium).
Abbracchio, Maria P. ; Verderio, Claudia. / Pathophysiological roles of P2 receptors in glial cells. Novartis Foundation Symposium. Vol. 276 2006. pp. 91-103 (Novartis Foundation Symposium).
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