Format

Send to

Choose Destination
Dis Model Mech. 2015 Jan;8(1):57-63. doi: 10.1242/dmm.018143. Epub 2014 Nov 14.

Untangling dopamine-adenosine receptor-receptor assembly in experimental parkinsonism in rats.

Author information

1
Unitat de Farmacologia, Departament Patologia i Terapèutica Experimental, Facultat de Medicina, IDIBELL-Universitat de Barcelona, L'Hospitalet de Llobregat, 08907 Barcelona, Spain.
2
Institut de Génomique Fonctionnelle, CNRS, UMR5203, Montpellier, France. INSERM, U.661, Montpellier and Université Montpellier 1,2, Montpellier, F-34094, France.
3
IRIBHM, Université Libre de Bruxelles, B1070 Brussels, Belgium.
4
Department of Anatomy, Hokkaido University School of Medicine, Sapporo 060-8638, Japan.
5
Cisbio Bioassays, 30200 Codolet, France.
6
Instituto de Investigación en Discapacidades Neurológicas (IDINE), Dept Ciencias Médicas, Facultad de Medicina, Universidad Castilla-La Mancha, 02006 Albacete, Spain.
7
Institut de Génomique Fonctionnelle, CNRS, UMR5203, Montpellier, France. INSERM, U.661, Montpellier and Université Montpellier 1,2, Montpellier, F-34094, France. tdurroux@igf.cnrs.fr fciruela@ub.edu.
8
Unitat de Farmacologia, Departament Patologia i Terapèutica Experimental, Facultat de Medicina, IDIBELL-Universitat de Barcelona, L'Hospitalet de Llobregat, 08907 Barcelona, Spain. tdurroux@igf.cnrs.fr fciruela@ub.edu.

Abstract

Parkinson's disease (PD) is a dopaminergic-related pathology in which functioning of the basal ganglia is altered. It has been postulated that a direct receptor-receptor interaction - i.e. of dopamine D2 receptor (D2R) with adenosine A2A receptor (A2AR) (forming D2R-A2AR oligomers) - finely regulates this brain area. Accordingly, elucidating whether the pathology prompts changes to these complexes could provide valuable information for the design of new PD therapies. Here, we first resolved a long-standing question concerning whether D2R-A2AR assembly occurs in native tissue: by means of different complementary experimental approaches (i.e. immunoelectron microscopy, proximity ligation assay and TR-FRET), we unambiguously identified native D2R-A2AR oligomers in rat striatum. Subsequently, we determined that, under pathological conditions (i.e. in a rat PD model), D2R-A2AR interaction was impaired. Collectively, these results provide definitive evidence for alteration of native D2R-A2AR oligomers in experimental parkinsonism, thus conferring the rationale for appropriate oligomer-based PD treatments.

KEYWORDS:

Immunoelectron microscopy; Oligomerization; Parkinson’s disease; Proximity ligation assay; TR-FRET

PMID:
25398851
PMCID:
PMC4283650
DOI:
10.1242/dmm.018143
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center