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Canals, M., Marcellino, D., Fanelli, F., Ciruela, F., de Benedetti, P., Goldberg, S.R., Neve, K., Fuxe, K., Agnati, L.F., Woods, A.S., Ferré, S., Lluis, C., Bouvier, M. and Franco, R. (2003) Adenosine A_2A-dopamine D₂ receptor-receptor heteromerization: Qualitative and quantitative assessment by fluorescence and bioluminescence energy transfer. Journal of Biological Chemistry, 278, 46741-46749. doi:10.1074/jbc.M306451200

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• TITLE: Changes in A2A adenosine receptor parameters in patients affected by bipolar disorders: Correlation with antipsychotic dosage and severity of illness

  AUTHORS: Maria Letizia Trincavelli, Simona Daniele, Antonio Ciapparelli, Mario Catena Dell’Osso, Gabriele Massimetti, Donatella Marazziti, Liliana Dell’Osso, Claudia Martini

  KEYWORDS: Bipolar Disorders; Human Platelets; A2A Adenosine Receptors; Typical Antipsychotics; Severity Of Illness; A2A/D2 Functional Interaction

  JOURNAL NAME: Open Journal of Psychiatry, Vol.2 No.1, December 31, 2011

  ABSTRACT: Typical antipsychotics, potent D2 dopamine receptor antagonists, are the most commonly used drugs in the treatment of bipolar disorders. In the central nervous system, the discovery of antagonistic interactions between A2A adenosine receptors and D2 dopamine receptors suggests that the adenosine system may be involved in the pathogenesis of different psychiatric disorders and in the therapeutic effectiveness of antipsychotic drugs. Previously, we have demonstrated an increase in A2A receptor expression and agonist affinity in platelets from psychotic patients treated with haloperidol. This result suggests that there is also a structural and functional interaction between A2A and D2 receptors in peripheral cells. In this work, we investigated the effect of different doses of typical drugs on A2A adenosine receptor binding and correlated these parameters with the severity of symptoms. We demonstrated, for the first time, that there was a strong correlation between A2A receptor affinity constant values (Kd) and drug doses in psychotic patients with a moderate severity of illness and moderate psychotic symptoms. The correlation was completely lost in patients with severe illness and severe psychotic symptoms. These results demonstrated that in platelets of patients affected by psychosis, typical antipsychotics modulated A2A receptor binding parameters; this regulation is dependent on the degree of D2 receptor occupancy in relation to the severity of psychotic symptoms, suggesting A2A receptors are a peripheral marker for individual therapy effectiveness.