Increase in the number, G protein coupling, and efficiency of facilitatory adenosine A2A receptors in the limbic cortex, but not striatum, of aged rats.
Adenosine's effects result from a balanced activation of inhibitory A1 and facilitatory A2A receptors. Because in aged animals there is an increased number of A2A receptors, we now compared the efficiency of A2A receptors in cortical and striatal preparations of young adult (6-week-old) and aged (2-year-old) rats. In cortical, in contrast to striatal, membranes from aged rats, A2A receptors were more tightly coupled to G proteins, because 5'-guanylylimidodiphosphate (100 microM) increased by 321% the Ki of the A2A agonist CGS21680 as a displacer of binding of the A2A antagonist [3H]ZM241385 (1 nM), compared with a 112% increase in young rats. In cortical slices, CGS21680 (30-1,000 nM) was virtually devoid of effect on cyclic AMP accumulation in young rats but increased cyclic AMP accumulation with an EC50 of 153 nM in aged rats, whereas the efficiency of CGS21680 was similar in striatal slices of young and aged rats. CGS21680 (30 nM) was virtually devoid of effect on acetylcholine release from hippocampal CA1 slices of young rats but caused a 55% facilitation in aged rats. These results show that the number of A2A receptors, their coupling to G proteins, and their efficiency are enhanced in the limbic cortex of aged rats, suggesting a greater involvement of facilitation in adenosine responses.
Lopes
L V
LV
Laboratory of Neurosciences, Faculty of Medicine, University of Lisbon, Lisboa, Portugal.
Cunha
R A
RA
Ribeiro
J A
JA
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000254:growth & development / Q000378:metabolism*; D003342:Corpus Striatum / Q000254:growth & development / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D018891:Dentate Gyrus / Q000254:growth & development / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D007700:Kinetics; D008032:Limbic System / Q000254:growth & development / Q000378:metabolism; D008297:Male; D009928:Organ Specificity; 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*; D014227:Triazines / Q000493:pharmacokinetics; D014230:Triazoles / Q000493:pharmacokinetics; D014316:Tritium
D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; D014316:Tritium; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000241:Adenosine