Upregulation of A2A adenosine receptors in platelets from patients affected by bipolar disorders under treatment with typical antipsychotics.

Abstract Antipsychotic drugs, potent dopamine receptor antagonists, are commonly used in the treatment of psychotic and affective illness. The discovery of antagonistic interactions between A 2A adenosine receptors (ARs) and D 2 dopamine receptors (DRs) in the central nervous system suggests that the adenosine system may be involved in the pathogenesis of psychiatric and neurological disorders. In the present study, we demonstrated for the first time that human platelets co-express A 2A ARs and D 2 DRs assembled into an heteromeric complexes. We also investigated the effects of chronic treatment with either typical or atypical antipsychotics on A 2A AR binding parameters and receptors responsiveness in human platelets from patients affected by bipolar disorder. Chronic administration of typical antipsychotics induced a significant upregulation of A 2A AR binding sites. Since no effects on A 2A AR were obtained following “in vitro” platelet treatment with a typical antipsychotic (haloperidol), we could exclude a direct effect of the drug on A 2A AR at the peripheral level. Moreover, typical antipsychotics induced a significant increase in the agonist potency to mediate A 2A AR–G protein coupling. On the contrary, chronic treatment with atypical antipsychotics did not induce any significant alterations in A 2A AR equilibrium binding parameters and receptor responsiveness suggesting that typical but not atypical antipsychotic drugs induced a selective modification of A 2A AR binding parameters in human platelets. These results are in accordance with the literature data describing the selective A 2A AR upregulation induced by typical antipsychotics in human striatum suggesting platelets as a peripheral model of the interactions between adenosine and dopamine system occurring in the central nervous system.