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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

1999; Wiley; Volume: 73; Issue: 4 Linguagem: Inglês

10.1046/j.1471-4159.1999.731733.x

1471-4159

Luı́sa V. Lopes, Rodrigo A. Cunha, Joaquim A. Ribeiro,

Pharmacological Receptor Mechanisms and Effects

Abstract : Adenosine's effects result from a balanced activation of inhibitory A 1 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 (6‐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 μ M ) increased by 321% the K i of the A 2A agonist CGS21680 as a displacer of binding of the A 2A antagonist [ 3 H]ZM241385 (1 n M ), compared with a 112% increase in young rats. In cortical slices, CGS21680 (30‐1,000 n M ) was virtually devoid of effect on cyclic AMP accumulation in young rats but increased cyclic AMP accumulation with an EC 50 of 153 n M in aged rats, whereas the efficiency of CGS21680 was similar in striatal slices of young and aged rats. CGS21680 (30 n M ) 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.