Trafficking of adenosine A2A and dopamine D2 receptors

An interaction between adenosine A(2A) and dopamine D-2 receptors has been demonstrated previously. It is generally found that agonist treatment internalizes receptors, including A(2A) and D-2, whereas less is known of the long-term effects involved in the agonist-mediated trafficking of A(2A) and D-2 receptors. Furthermore, the possible influence of the antagonists on receptor trafficking is still undefined. The present studies focus on the long-term effects of A(2A) and D-2 agonist and D-2 antagonist treatments on both A and D receptor trafficking studied at three different time intervals-3, 15, and 24 h. In addition, with the fluorescence resonance energy transfer technique, formation of heteromeric A(2A) and D-2 receptor complexes was shown in the cotransfected CHO cell line. Confocal microscopy analysis showed that a 3-h treatment with the D-2 agonist induced coaggregation of A(2A)/D-2 receptors. These A(2A)/D-2 receptor coaggregates internalized after 15 h with a recruitment of the receptors back to the cell membrane after 24 h. In contrast to the effects of the agonist treatment, a 3-h treatment with the D-2-like antagonist raclopride increased both A(2A) and D-2 immunoreactivity, indicating that the D-2 antaconist stabilizes the D-2 receptor and thereby reduces the internalization of both of the A(2A) and D-2 receptors. Taken together, an activation of either A(2A) and D-2 receptor or blockade of D-2 receptors will cause long-lasting changes in A(2A) and D-2 receptor trafficking.