Blockade of A2A adenosine receptors prevents basic fibroblast growth factor-induced reactive astrogliosis in rat striatal primary astrocytes

Previous literature data show that blockade of A(2A) adenosine receptors via selective antagonists induces protection in various models of neurodegenerative diseases. The mechanisms underlying this effect are still largely unknown. Since it is known that excessive reactive astrogliosis is a factor contributing to cell death in diseases characterized by neurodegenerative events, the present study has been aimed at determining whether selective A(2A) receptor antagonists can counteract the formation of reactive astrocytes induced in vitro by basic fibroblast growth factor (bFGF), a typical trigger of this reaction. Exposure of primary rat striatal astrocytes to the selective A(2A) antagonist SCH58261 resulted in concentration-dependent abolition of bFGF induction of astrogliosis in vitro. This effect could also be reproduced with the chemically unrelated A(2A) antagonist KW-6002. The direct activation of A(2A) adenosine receptors by selective receptor agonists was not sufficient per se to induce astrogliosis, suggesting that the A(2A) receptor needs to act in concert with other bFGF-induced genes to trigger the formation of reactive astrocytes. These results provide a mechanism at the basis of the neuroprotection induced by A(2A) receptor antagonists in models of brain damage and highlight this adenosine receptor subtype as a novel target for the pharmacological modulation of the gliotic reaction. (C) 2003 Wiley-Liss, Inc.