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Activation of P2X(7) receptors stimulates the expression of P2Y(2) receptor mRNA in astrocytes cultured from rat brain
- Source :
- International journal of immunopathology and pharmacology. 20(2)
- Publication Year :
- 2007
-
Abstract
- Under pathological conditions brain cells release ATP at concentrations reported to activate P2X7 ionotropic receptor subtypes expressed in both neuronal and glial cells. In the present study we report that the most potent P2X7 receptor agonist BzATP stimulates the expression of the metabotropic ATP receptor P2Y2 in cultured rat brain astrocytes. In other cell types several kinds of stimulation, including stress or injury, induce P2Y2 expression that, in turn, is involved in different cell reactions. Similarly, it has recently been found that in astrocytes and astrocytoma cells P2Y2 sites can trigger neuroprotective pathways through the activation of several mechanisms, including the induction of genes for antiapoptotic factors, neurotrophins, growth factors and neuropeptides. Here we present evidence that P2Y2 mRNA expression in cultured astrocytes peaks 6 h after BzATP exposure and returns to basal levels after 24 h. This effect was mimicked by high ATP concentrations (1 mM) and was abolished by P2X7-antagonists oATP and BBG. The BzATP-evoked P2Y2 receptor up-regulation in cultured astrocytes was coupled to an increased UTP-mediated intracellular calcium response. This effect was inhibited by oATP and BBG and by P2Y2siRNA, thus supporting evidence of increased P2Y2 activity. To further investigate the mechanisms by which P2X7 receptors mediated the P2Y2 mRNA up-regulation, the cells were pre-treated with the chelating agent EGTA, or with inhibitors of mitogen-activated kinase (MAPK) (PD98059) or protein kinase C, (GF109203X). Each inhibitor significantly reduced the extent to which BzATP induced P2Y2 mRNA. Both BzATP and ATP (1 mM) increased ERK1/2 activation. P2X7-induced ERK1/2 phosphorylation was unaffected by pre-treatment of astrocytes with EGTA whereas it was inhibited by GF109203X. Phorbol-12-myristate-13-acetate (PMA), an activator of PKCs, rapidly increased ERK1/2 activation. We conclude that activation of P2X7 receptors in astrocytes enhances P2Y2 mRNA expression by a mechanism involving both calcium influx and PKC/MAPK signalling pathways.
- Subjects :
- MAPK/ERK pathway
Immunology
Stimulation
Calcium in biology
Receptors, Purinergic P2Y2
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Adenosine Triphosphate
Immunology and Allergy
Animals
RNA, Messenger
Receptor
Protein kinase C
Cells, Cultured
Pharmacology
Chemistry
Kinase
Receptors, Purinergic P2
Brain
Cell biology
Rats
EGTA
Metabotropic receptor
Gene Expression Regulation
030220 oncology & carcinogenesis
Astrocytes
Receptors, Purinergic P2X7
030215 immunology
Subjects
Details
- ISSN :
- 03946320
- Volume :
- 20
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- International journal of immunopathology and pharmacology
- Accession number :
- edsair.doi.dedup.....f34ed3e9f3f8d7d4be09cadf88734e93