Receptor cross-talk: haloperidol treatment enhances A2A adenosine receptor functioning in a transfected cell model
| Autor: | Anna Panighini, Karl-Norbert Klotz, Roberto Maggio, Francesca Novi, Claudia Martini, Simona Daniele, Serena Cuboni, Mario Catena Dell'Osso, Maria Letizia Trincavelli |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_specialty
business.industry Cell Biology Purinergic signalling Pharmacology Adenosine A3 receptor Adenosine receptor Adenosine Cellular and Molecular Neuroscience Adenosine A1 receptor Endocrinology Dopamine receptor Internal medicine Dopamine receptor D2 Medicine Original Article business Molecular Biology Adenosine A2B receptor medicine.drug |
| Popis: | A2A adenosine receptors are considered an excellent target for drug development in several neurological and psychiatric disorders. It is noteworthy that the responses evoked by A2A adenosine receptors are regulated by D2 dopamine receptor ligands. These two receptors are co-expressed at the level of the basal ganglia and interact to form functional heterodimers. In this context, possible changes in A2A adenosine receptor functional responses caused by the chronic blockade/activation of D2 dopamine receptors should be considered to optimise the therapeutic effectiveness of dopaminergic agents and to reduce any possible side effects. In the present paper, we investigated the regulation of A2A adenosine receptors induced by antipsychotic drugs, commonly acting as D2 dopamine receptor antagonists, in a cellular model co-expressing both A2A and D2 receptors. Our data suggest that the treatment of cells with the classical antipsychotic haloperidol increased both the affinity and responsiveness of the A2A receptor and also affected the degree of A2A–D2 receptor heterodimerisation. In contrast, an atypical antipsychotic, clozapine, had no effect on A2A adenosine receptor parameters, suggesting that the two classes of drugs have different effects on adenosine–dopamine receptor interaction. Modifications to A2A adenosine receptors may play a significant role in determining cerebral adenosine effects during the chronic administration of antipsychotics in psychiatric diseases and may account for the efficacy of A2A adenosine receptor ligands in pathologies associated with dopaminergic system dysfunction. Electronic supplementary material The online version of this article (doi:10.1007/s11302-010-9201-z) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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