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Cyclo-oxygenase-2 mediates P2Y receptor-induced reactive astrogliosis.

Brambilla, R; Burnstock, G; Bonazzi, A; Ceruti, S; Cattabeni, F; Abbracchio, MP; (1999) Cyclo-oxygenase-2 mediates P2Y receptor-induced reactive astrogliosis. Br J Pharmacol , 126 (3) pp. 563-567. 10.1038/sj.bjp.0702333.

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Abstract

Excessive cyclo-oxygenase-2 (COX-2) induction may play a role in chronic neurological diseases characterized by inflammation and astrogliosis. We have previously identified an astroglial receptor for extracellular nucleotides, a P2Y receptor, whose stimulation leads to arachidonic acid (AA) release, followed, 3 days later, by morphological changes resembling reactive astrogliosis. Since COX-2 may be upregulated by AA metabolites, we assessed a possible role for COX-2 in P2Y receptor-mediated astrogliosis. A brief challenge of rat astrocytes with the ATP analogue alpha,beta-methylene ATP (alpha,beta(me)ATP) resulted, 24 h later, in significantly increased COX-2 expression. The selective COX-2 inhibitor NS-398 completely abolished alpha,beta(me)ATP-induced astrocytic activation. Constitutive astroglial COX-1 or COX-2 did not play any role in purine-induced reactive astrogliosis. PGE2, a main metabolite of COX-2, also induced astrocytic activation. These data suggest that a P2Y receptor mediates reactive astrogliosis via induction of COX-2. Antagonists selective for this receptor may counteract excessive COX-2 activation in both acute and chronic neurological diseases.

Type: Article
Title: Cyclo-oxygenase-2 mediates P2Y receptor-induced reactive astrogliosis.
Location: England
DOI: 10.1038/sj.bjp.0702333
Keywords: Adenosine Triphosphate, Animals, Aspirin, Astrocytes, Cells, Cultured, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Cyclooxygenase Inhibitors, Dinoprostone, Dose-Response Relationship, Drug, Gliosis, Isoenzymes, Nitrobenzenes, Prostaglandin D2, Prostaglandin-Endoperoxide Synthases, Rats, Receptors, Purinergic P2, Sulfonamides, Time Factors
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
URI: http://discovery.ucl.ac.uk/id/eprint/22219
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