Autocrine activation of adenosine A 1 receptors blocks D 1A but not D 1B dopamine receptor desensitization

Adenosine is known to modulate dopamine responses in several brain areas. Here, we show that tonic activation of adenosine receptors is able to impede desensitization of D 1 dopamine receptors. As measured by cAMP accumulation in transfected COS‐7 cells, long‐term exposure to dopamine agonists promoted desensitization of D 1B receptor but not that of D 1A receptor. The inability of D 1A receptor to desensitize was a result of the adenosine present in culture medium acting through activation of adenosine A1 receptors. Cell incubation with either adenosine deaminase, CGS‐15943, a generic adenosine receptor antagonist, or the A 1 antagonist DPCPX restored the long‐term desensitization time‐course of D 1A receptors. In Ltk cells stably expressing A1 adenosine receptors and D 1A dopamine receptors, pre‐treatment of cells with R (–)‐PIA, a full A1 receptor agonist, did not significantly inhibit the acute increase in cAMP levels induced by D1 receptor agonists, but blocked desensitization of D 1A receptors. However, simultaneous activation of A 1 and D 1A receptors promoted a delayed D 1A receptor desensitization. This suggests that functional interaction between A1 and D 1A receptors may depend on the activation kinetics of components regulating D1 receptor responses, acting differentially on D 1A and D 1B receptors.