Oligomerization of G protein-coupled receptors has become a very important issue in a present molecular pharmacology. In the present study the level of the serotonin 5-HT(2A) and the dopamine D(2) receptor interactions have been studied since it may have a key significance in understanding the mechanism of action of drugs used to treat schizophrenia. With the use of fluorescence resonance energy transfer we demonstrated that the serotonin 5-HT(2A) receptors form homo- and hetero-dimers with the dopamine D(2) receptors and polymorphism H452Y within the 5-HT(2A) receptor, implicated as a cause of altered response to antipsychotic treatment, disturbs both processes. Clozapine affected the hetero-dimers (5-HT(2A)H452Y/D(2)) complexes and increased the otherwise weakened dimerization to the value observed for combination of both wild type receptors, and had no effect on the serotonin receptor homo-dimers (5-HT(2A)H452Y/5-HT(2A)), while haloperidol has restored the weakened interaction within homo-complexes and did not effect the hetero-complexes. The obtained data suggest that H452Y polymorphism has an influence not only on the level of constitutive oligomerization of investigated receptors but also it changes their pharmacological properties within both homo- and hetero-complexes.
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