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Prostaglandin E 2 Impairs P2Y 2 /P2Y 4 Receptor Signaling in Cerebellar Astrocytes via EP3 Receptors
Ist Teil von
Frontiers in pharmacology, 2017, Vol.8, p.937
Ort / Verlag
Switzerland
Erscheinungsjahr
2017
Link zum Volltext
Quelle
EZB Electronic Journals Library
Beschreibungen/Notizen
Prostaglandin E
(PGE
) is an important bioactive lipid that accumulates after tissue damage or inflammation due to the rapid expression of cyclooxygenase 2. PGE
activates specific G-protein coupled EP receptors and it mediates pro- or anti-inflammatory actions depending on the cell-context. Nucleotides can also be released in these situations and they even contribute to PGE
production. We previously described the selective impairment of P2Y nucleotide signaling by PGE
in macrophages and fibroblasts, an effect independent of prostaglandin receptors but that involved protein kinase C (PKC) and protein kinase D (PKD) activation. Considering that macrophages and fibroblasts influence inflammatory responses and tissue remodeling, a similar mechanism involving P2Y signaling could occur in astrocytes in response to neuroinflammation and brain repair. We analyzed here the modulation of cellular responses involving P2Y
/P2Y
receptors by PGE
in rat cerebellar astrocytes. We demonstrate that PGE
inhibits intracellular calcium responses elicited by UTP in individual cells and that inhibiting this P2Y signaling impairs the astrocyte migration elicited by this nucleotide. Activation of EP3 receptors by PGE
not only impairs the calcium responses but also, the extracellular regulated kinases (ERK) and Akt phosphorylation induced by UTP. However, PGE
requires epidermal growth factor receptor (EGFR) transactivation in order to dampen P2Y signaling. In addition, these effects of PGE
also occur in a pro-inflammatory context, as evident in astrocytes stimulated with bacterial lipopolysaccharide (LPS). While we continue to investigate the intracellular mechanisms responsible for the inhibition of UTP responses, the involvement of novel PKC and PKD in cerebellar astrocytes cannot be excluded, kinases that could promote the internalization of P2Y receptors in fibroblasts.
Sprache
Englisch
Identifikatoren
ISSN: 1663-9812
eISSN: 1663-9812
Titel-ID: cdi_pubmed_primary_29311938
Format
–
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