Adenosine A2 receptors: selective localization in the human basal ganglia and alterations with disease.
Adenosine A2 receptors were labeled and visualized by autoradiography in tissue sections of the human brain using the A2-selective agonist ligand [3H](2-p-(2-carboxyethyl)phenylamino)-5'-N-carboxamidoadenosine (CGS 21680). The binding of this ligand was of high affinity, reversible, and was blocked by adenosine A2 agents. Autoradiographic mapping of adenosine A2 sites revealed them to be exclusively restricted to the caudate nucleus, putamen, nucleus accumbens, olfactory tubercle and the lateral segment of the globus pallidus. The densities of adenosine A2 receptors in other brain areas did not differ from background levels. This selective localization prompted us to study the consequences of neurodegenerative diseases such as Parkinson's disease and Huntington's chorea on the densities and localization of these sites in the basal ganglia. In Parkinson's disease the density of adenosine A2 binding sites was comparable to that seen in control cases. In contrast, density values of A2 sites were dramatically decreased, compared to control values, in the basal ganglia of patients with Huntington's chorea. Similar losses of A2 receptors were observed in the guinea-pig striatum after local application of quinolinic acid while lesioning of the dopaminergic neurons was without effect. All these results taken together suggest that adenosine A2 receptors are localized on striatal output neurons which degenerate in Huntington's chorea.
Martinez-Mir
M I
MI
Preclinical Research, Sandoz Pharma Ltd, Basel, Switzerland.
Probst
A
A
Palacios
J M
JM
D000241:Adenosine / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001479:Basal Ganglia / Q000737:chemistry* / Q000473:pathology; D003342:Corpus Striatum / Q000737:chemistry / Q000473:pathology; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration; D009928:Organ Specificity; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000633:toxicity; D011983:Receptors, Purinergic / Q000032:analysis*
D011805:Quinolinic Acids; D011983:Receptors, Purinergic; D016627:Oxidopamine; D017378:Quinolinic Acid; D000241:Adenosine