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Cyclo‐oxygenase‐2 mediates P2Y receptor‐induced reactive astrogliosis
Author(s) -
Brambilla Roberta,
Burnstock Geoffrey,
Bonazzi Albino,
Ceruti Stefania,
Cattabeni Flaminio,
Abbracchio Maria P
Publication year - 1999
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702333
Subject(s) - astrogliosis , p2y receptor , p2 receptor , receptor , astrocyte , pharmacology , chemistry , endocrinology , medicine , biology , agonist , biochemistry , central nervous system
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. PGE 2 , 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. British Journal of Pharmacology (1999) 126 , 563–567; doi: 10.1038/sj.bjp.0702333