Adenosine A2A receptors and neuroprotection.
The adenosine A2A receptor subtype is one of the four adenosine receptors that have been identified in the mammalian organism. In addition to being found in blood vessels, platelets and polymorphonuclear leukocytes, the A2A receptors are abundant in the central nervous system, especially in the striatum. The recent development of selective A2A receptor ligands, in particular of receptor antagonists, makes it possible to elucidate the function of A2A receptors in normal and altered conditions. Pharmacological studies have shown that A2A receptor antagonists are potentially effective for treatment of neurodegenerative processes such as Parkinson's disease. Their activity is attributed to the close anatomical and functional links between A2A receptors and dopaminergic pathways in the basal ganglia. More recently, A2A receptor antagonists have proved to be active in models of cerebral ischemia. While the mechanisms underlying the role of A2A receptors in the hypoxia/ ischemia processes remains to be clarified, it is recognized that A2A receptor antagonists counteract the effects of excitatory aminoacids, which are massively released after cerebral ischemia. Another function of A2A receptors is related to protection from seizures, but further studies are needed to elucidate their specific interaction, if any, with neuronal excitability. Altogether, the great advance recently made with the discovery of selective A2A receptor ligands provides increasing information on the function of A2A receptors and opens new perspectives for treatment of neurological disorders.
Ongini
E
E
Schering-Plough Research Institute, Milan, Italy. ongini.sch.pl@science-park.spr.it
Adami
M
M
Ferri
C
C
Bertorelli
R
R
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D001927:Brain Diseases / Q000188:drug therapy / Q000503:physiopathology*; D002545:Brain Ischemia / Q000188:drug therapy / Q000503:physiopathology; D004298:Dopamine / Q000502:physiology; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy / Q000503:physiopathology; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D012640:Seizures / Q000188:drug therapy / Q000503:physiopathology
D018696:Neuroprotective Agents; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D000241:Adenosine; D004298:Dopamine