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

• Published in: British journal of pharmacology Vol. 126; no. 3; pp. 563 - 567
• Main Authors: Brambilla, Roberta, Burnstock, Geoffrey, Bonazzi, Albino, Ceruti, Stefania, Cattabeni, Flaminio, Abbracchio, Maria P
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.1999; Nature Publishing
• Subjects: a,^b-Methylene ATP; Adenosine Triphosphate - analogs & derivatives; Adenosine Triphosphate - pharmacology; Animals; Aspirin - pharmacology; Astrocytes - cytology; Astrocytes - drug effects; Astrocytes - pathology; astrogliosis; ATP; Biological and medical sciences; Cells, Cultured; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - pharmacology; cyclo‐oxygenase‐2; Dinoprostone - pharmacology; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Gliosis - enzymology; Gliosis - pathology; Gliosis - physiopathology; inflammation; Isoenzymes - drug effects; Isoenzymes - physiology; Isolated neuron and nerve. Neuroglia; Nitrobenzenes - pharmacology; P2Y receptors; Prostaglandin D2 - pharmacology; Prostaglandin-Endoperoxide Synthases - drug effects; Prostaglandin-Endoperoxide Synthases - physiology; Rats; Receptors, Purinergic P2 - physiology; Special Reports; Sulfonamides - pharmacology; Time Factors; Vertebrates: nervous system and sense organs; Cell culture; Prostaglandin-endoperoxide synthase; Rat; Enzyme; Isozyme; Neuroglia; Rodentia; Prostaglandin E2; P2 Purinergic receptor; Inflammation; Astrocyte; In vitro; Vertebrata; Mammalia; Gliosis; Animal; Oxidoreductases; Nervous tissue; ATP
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0702333

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. British Journal of Pharmacology (1999) 126, 563–567; doi:10.1038/sj.bjp.0702333