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 journalArticle

69 Citations (Scopus)

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
Pages (from-to)563-567
Number of pages5
JournalBritish Journal of Pharmacology
Volume126
Issue number3
DOIs
StatePublished - Feb 28 1999
Externally publishedYes

Fingerprint

Prostaglandin-Endoperoxide Synthases
Arachidonic Acid
Chronic Disease
Adenosine Triphosphate
Cyclooxygenase Inhibitors
Dinoprostone
Astrocytes
Nucleotides
Inflammation

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

Cite this

Brambilla, R., Burnstock, G., Bonazzi, A., Ceruti, S., Cattabeni, F., & Abbracchio, M. P. (1999). Cyclo-oxygenase-2 mediates P2Y receptor-induced reactive astrogliosis. British Journal of Pharmacology, 126(3), 563-567. https://doi.org/10.1038/sj.bjp.0702333

Cyclo-oxygenase-2 mediates P2Y receptor-induced reactive astrogliosis. / Brambilla, Roberta; Burnstock, Geoffrey; Bonazzi, Albino; Ceruti, Stefania; Cattabeni, Flaminio; Abbracchio, Maria P.

In: British Journal of Pharmacology, Vol. 126, No. 3, 28.02.1999, p. 563-567.

Research output: Contribution to journalArticle

Brambilla, R, Burnstock, G, Bonazzi, A, Ceruti, S, Cattabeni, F & Abbracchio, MP 1999, 'Cyclo-oxygenase-2 mediates P2Y receptor-induced reactive astrogliosis', British Journal of Pharmacology, vol. 126, no. 3, pp. 563-567. https://doi.org/10.1038/sj.bjp.0702333
Brambilla, Roberta ; Burnstock, Geoffrey ; Bonazzi, Albino ; Ceruti, Stefania ; Cattabeni, Flaminio ; Abbracchio, Maria P. / Cyclo-oxygenase-2 mediates P2Y receptor-induced reactive astrogliosis. In: British Journal of Pharmacology. 1999 ; Vol. 126, No. 3. pp. 563-567.
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