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Direct visualization of adenosine A 2A and dopamine D 2L receptor oligomers in a neuronal cell model
Author(s) -
Vidi PierreAlexandre,
Chemel Benjamin R.,
Watts Val J.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.723.3
Subject(s) - bimolecular fluorescence complementation , dopamine , agonist , chemistry , dopamine receptor , receptor , microbiology and biotechnology , dopamine receptor d2 , biophysics , biology , neuroscience , biochemistry , yeast
Dopamine D 2 and adenosine A 2A receptors are co‐expressed in GABAergic neurons in the basal ganglia where they antagonistically regulate adenylyl cyclase activity. Interactions between D 2 and A 2A are thought to play an important role in drug addiction and in the pharmacotherapy of Parkinson's disease. Molecular mechanisms may involve the formation of receptor oligomers signaling to alternative pathways. D 2 and A 2A have been shown to form homo‐ and heterooligomers both in recombinant cells and in native brain tissues. However, the stoichiometry of these complexes, as well as the regulation or their formation (notably by ligands) remain to be characterized. We have used bimolecular fluorescence complementation (BiFC) for direct visualization of A 2A homodimers and A 2A ‐ D 2 heterodimers in a neuronal cell model. Initial studies revealed that the receptor‐BiFC fusion proteins remained functional. Preliminary experiments using multicolor BiFC indicated that prolonged exposure to D 2 antagonist spiperone promotes A 2A ‐ D 2 dimerization whereas D 2 agonist quinpirole treatment upregulates A 2A homodimerization. In addition, studies combining BiFC with FRET provided evidence for the formation of higher‐order A 2A D 2 oligomers. This project was funded by Purdue University and NIMH grant award MH060397 to VJW.