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

Roberta Brambilla, Geoffrey Burnstock, Albino Bonazzi, Stefania Ceruti, Flaminio Cattabeni, Maria P. Abbracchio

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

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 α,β-methylene ATP (α,βmeATP) resulted, 24 h later, in significantly increased COX-2 expression. The selective COX-2 inhibitor NS-398 completely abolished α,βmeATP-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.

Original languageEnglish (US)
Pages (from-to)563-567
Number of pages5
JournalBritish Journal of Pharmacology
Volume126
Issue number3
DOIs
StatePublished - 1999
Externally publishedYes

Keywords

  • Astrogliosis
  • ATP
  • Cyclo-oxygenase-2
  • Inflammation
  • P2Y receptors

ASJC Scopus subject areas

  • Pharmacology

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