Modification of A1 and A2a adenosine receptor binding in aged striatum, hippocampus and cortex of the rat.
Age-related changes of A1 and A2a adenosine receptor binding characteristics were investigated in three regions of the rat brain using the A1 selective antagonist [3H]DPCPX, and the A2a selective agonist [3H]CGS 21680. The density of A1 binding sites in aged rats (24 months) was decreased by 33% in the hippocampus and by 60% in the cortex and was unchanged in the striatum when compared with young adult rats (6 weeks), with no change in KD. There were also age-related changes in the density of A2a binding sites: in the cortex, there was a 94% increase in the number of [3H]CGS 21680 binding sites in aged rats compared with young rats, and a similar tendency was observed in the hippocampus (32% increase in A2a binding sites in aged rats), with no change in KD; in the striatum there was a tendency for a decrease (22%) in the number of [3H]CGS 21680 binding sites in aged rats, and a decrease in KD. These results suggest that there are age-related changes in the balance between inhibitory A1- and excitatory A2a-adenosine receptor-mediated actions, which vary in different brain areas: in the cortex and hippocampus, the balance might be shifted towards adenosine-mediated excitatory actions, since there is an increase in the number of A2a receptors and a decrease in the number of A1 receptors upon ageing. In contrast, in the striatum, the A1/A2a ratio might be only slightly affected upon ageing.
Cunha
R A
RA
Lab. Pharmacology, Gulbenkian Institute of Science, Oeiras, Portugal.
Constantino
M C
MC
Sebastião
A M
AM
Ribeiro
J A
JA
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D010627:Phenethylamines / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D014970:Xanthines / Q000378:metabolism
D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D014970:Xanthines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine