Untangling dopamine-adenosine receptor assembly in experimental parkinsonism in rats
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 D-2 receptor (D2R) with adenosine A(2A) receptor (A(2A)R) (forming D2R-A(2A)R oligomers) - fin...
| Authors: | , , , , , , , , , , , |
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| Format: | article |
| Status: | Published version |
| Publication Date: | 2015 |
| Country: | España |
| Institution: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repository: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/125691 |
| Online Access: | https://hdl.handle.net/2445/125691 |
| Access Level: | Open access |
| Keyword: | Malaltia de Parkinson Adenosina Dopamina Parkinson's disease Adenosine Dopamine |
| Summary: | 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 D-2 receptor (D2R) with adenosine A(2A) receptor (A(2A)R) (forming D2R-A(2A)R 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-A(2A)R 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-A(2A)R oligomers in rat striatum. Subsequently, we determined that, under pathological conditions (i.e. in a rat PD model), D2R-A(2A)R interaction was impaired. Collectively, these results provide definitive evidence for alteration of native D2R-A(2A)R oligomers in experimental parkinsonism, thus conferring the rationale for appropriate oligomer-based PD treatments. |
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