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Regulation of A 2A adenosine receptor expression and functioning following permanent focal ischemia in rat brain
Author(s) -
Trincavelli Maria L.,
Melani Alessia,
Guidi Sara,
Cuboni Serena,
Cipriani Sara,
Pedata Felicita,
Martini Claudia
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04990.x
Subject(s) - striatum , ischemia , adenosine receptor , adenosine a1 receptor , adenosine , receptor , adenosine a3 receptor , stimulation , neuroscience , cerebral cortex , medicine , brain ischemia , endocrinology , middle cerebral artery , biology , chemistry , dopamine , agonist
Ischemia, through modulation of adenosine receptors (ARs), may influence adenosine‐mediated‐cellular responses. In the present study, we investigated the modulation of rat A 2A receptor expression and functioning, in rat cerebral cortex and striatum, following in vivo focal ischemia (24 h). In cortex, middle cerebral artery occlusion did not induce any alterations in A 2A receptor binding and functioning. On the contrary, in striatum, a significant decrease in A 2A ligand affinity, associated with an increase in receptor density, were detected. In striatum, ischemia also induced a significant reduction both in G protein pool and in A 2A receptor‐G protein coupling. On the contrary, A 2A receptor functional responsiveness, measured as stimulation of adenylyl cyclise, was not affected by ischemia, suggesting receptor up‐regulation may represent a compensatory mechanism to maintain receptor functioning during cerebral damage. Immunohistochemical study showed that following 24 h middle cerebral artery occlusion, A 2A ARs were definitely expressed both on neurons and activated microglia in ischemic striatum and cortex, but were not detected on astrocytes. In the non‐ischemic hemisphere and in sham‐operated rats A 2A ARs were barely detected. Modifications of ARs may play a significant role in determining adenosine effects during ischemia and therefore should be taken into account when evaluating time‐dependent protective effects of specific A 2A active compounds.