title: Receptor crosstalk: haloperidol treatment enhances A(2A) adenosine receptor functioning in a transfected cell model.
abstract: A(2A) adenosine receptors are considered an excellent target for drug development in several neurological and psychiatric disorders. It is noteworthy that the responses evoked by A(2A) adenosine receptors are regulated by D(2) 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 A(2A) adenosine receptor functional responses caused by the chronic blockade/activation of D(2) 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 A(2A) adenosine receptors induced by antipsychotic drugs, commonly acting as D(2) dopamine receptor antagonists, in a cellular model co-expressing both A(2A) and D(2) receptors. Our data suggest that the treatment of cells with the classical antipsychotic haloperidol increased both the affinity and responsiveness of the A(2A) receptor and also affected the degree of A(2A)-D(2) receptor heterodimerisation. In contrast, an atypical antipsychotic, clozapine, had no effect on A(2A) adenosine receptor parameters, suggesting that the two classes of drugs have different effects on adenosine-dopamine receptor interaction. Modifications to A(2A) 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 A(2A) adenosine receptor ligands in pathologies associated with dopaminergic system dysfunction.
  
  
  BACKGROUND
  The online version of this article (doi:10.1007/s11302-010-9201-z) contains supplementary material, which is available to authorized users.
authors: Maria Letizia
authors: ML
authors: Trincavelli
authors: Serena
authors: S
authors: Cuboni
authors: Mario
authors: M
authors: Catena Dell'osso
authors: Roberto
authors: R
authors: Maggio
authors: Karl-Norbert
authors: KN
authors: Klotz
authors: Francesca
authors: F
authors: Novi
authors: Anna
authors: A
authors: Panighini
authors: Simona
authors: S
authors: Daniele
authors: Claudia
authors: C
authors: Martini