Regulation of A(2A) adenosine receptor expression and functioning following permanent focal ischemia in rat brain.
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.
Trincavelli
Maria L
ML
Department of Psychiatry, Neurobiology, Pharmacology and Biotechnology, University of Pisa, Pisa, Italy.
Melani
Alessia
A
Guidi
Sara
S
Cuboni
Serena
S
Cipriani
Sara
S
Pedata
Felicita
F
Martini
Claudia
C
D000241:Adenosine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D058908:Adenosine A2 Receptor Agonists; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000493:pharmacokinetics; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009460:Neurologic Examination; D010627:Phenethylamines / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D043683:Receptors, Adenosine A2 / Q000235:genetics / Q000378:metabolism*
D058908:Adenosine A2 Receptor Agonists; D010627:Phenethylamines; D043683:Receptors, Adenosine A2; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000241:Adenosine