title: 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 A2A adenosine receptors (ARs) and D2 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 A2A ARs and D2 DRs assembled into an heteromeric complexes. We also investigated the effects of chronic treatment with either typical or atypical antipsychotics on A2A 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 A2A AR binding sites. Since no effects on A2A AR were obtained following "in vitro" platelet treatment with a typical antipsychotic (haloperidol), we could exclude a direct effect of the drug on A2A AR at the peripheral level. Moreover, typical antipsychotics induced a significant increase in the agonist potency to mediate A2A AR-G protein coupling. On the contrary, chronic treatment with atypical antipsychotics did not induce any significant alterations in A2A AR equilibrium binding parameters and receptor responsiveness suggesting that typical but not atypical antipsychotic drugs induced a selective modification of A2A AR binding parameters in human platelets. These results are in accordance with the literature data describing the selective A2A 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.
authors.affiliation: Department of Psychiatry, Neurobiology, Pharmacology and Biotechnology, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy. cmartini@farm.unipi.it
authors.forename: Claudia
authors.initials: C
authors.lastname: Martini
authors.forename: Daniela
authors.initials: D
authors.lastname: Tuscano
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Trincavelli
authors.forename: Elisa
authors.initials: E
authors.lastname: Cerrai
authors.forename: Maria
authors.initials: M
authors.lastname: Bianchi
authors.forename: Antonio
authors.initials: A
authors.lastname: Ciapparelli
authors.forename: Lucioni
authors.initials: L
authors.lastname: Alessio
authors.forename: Letizia
authors.initials: L
authors.lastname: Novelli
authors.forename: Mario
authors.initials: M
authors.lastname: Catena
authors.forename: Antonio
authors.initials: A
authors.lastname: Lucacchini
authors.forename: Giovanni Battista
authors.initials: GB
authors.lastname: Cassano
authors.forename: Liliana
authors.initials: L
authors.lastname: Dell'Osso
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001667:Binding, Competitive / Q000187:drug effects; D001714:Bipolar Disorder / Q000097:blood* / Q000188:drug therapy*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006220:Haloperidol / Q000627:therapeutic use*; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D011869:Radioligand Assay; D043705:Receptor, Adenosine A2A / Q000187:drug effects* / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology; D012016:Reference Values; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D014150:Antipsychotic Agents; D043705:Receptor, Adenosine A2A; D017448:Receptors, Dopamine D2; D006220:Haloperidol