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 A, and facilitatory A(2A) receptors. Because in aged animals there is an increased number of A(2A) receptors, we now compared the efficiency of A(2A) receptors in cortical and striatal preparations of young adult (8-week-old) and aged (2-year-old) rats. In cortical, in contrast to striatal, membranes from aged rats, A(2A) receptors were more tightly coupled to G proteins, because 5'-guanylylimidodiphosphate (100 mu M) increased by 321% the K-i of the A(2A) agonist CGS21680 as a displacer of binding of the A(2A) antagonist [H-3]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 A(2A) 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.