Increase in the Number, G Protein Coupling, and Efficiency of Facilitatory Adenosine A_2A Receptors in the Limbic Cortex, but not Striatum, of Aged Rats

<jats:p> <jats:bold>Abstract</jats:bold> : Adenosine's effects result from a balanced activation of inhibitory A<jats:sub>1</jats:sub> and facilitatory A<jats:sub>2A</jats:sub> receptors. Because in aged animals there is an increased number of A<jats:sub>2A</jats:sub> receptors, we now compared the efficiency of A<jats:sub>2A</jats:sub> 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, A<jats:sub>2A</jats:sub> receptors were more tightly coupled to G proteins, because 5′‐guanylylimidodiphosphate (100 μ<jats:italic>M</jats:italic>) increased by 321% the <jats:italic>K</jats:italic><jats:sub>i</jats:sub> of the A<jats:sub>2A</jats:sub> agonist CGS21680 as a displacer of binding of the A<jats:sub>2A</jats:sub> antagonist [<jats:sup>3</jats:sup>H]ZM241385 (1 n<jats:italic>M</jats:italic>), compared with a 112% increase in young rats. In cortical slices, CGS21680 (30‐1,000 n<jats:italic>M</jats:italic>) was virtually devoid of effect on cyclic AMP accumulation in young rats but increased cyclic AMP accumulation with an EC<jats:sub>50</jats:sub> of 153 n<jats:italic>M</jats:italic> in aged rats, whereas the efficiency of CGS21680 was similar in striatal slices of young and aged rats. CGS21680 (30 n<jats:italic>M</jats:italic>) 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<jats:sub>2A</jats:sub> 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.</jats:p>