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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / pathology
  • Cell Membrane / metabolism
  • Corpus Striatum / metabolism
  • Disease Models, Animal
  • Dopamine / chemistry*
  • Fluorescence Resonance Energy Transfer
  • Humans
  • Immunohistochemistry
  • Ligands
  • Mice
  • Mice, Knockout
  • Microscopy, Immunoelectron
  • Oxidopamine / chemistry
  • Parkinsonian Disorders / drug therapy
  • Parkinsonian Disorders / metabolism*
  • Plasmids / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine / chemistry*
  • Receptors, Purinergic P1 / chemistry*


  • Ligands
  • Receptors, Dopamine
  • Receptors, Purinergic P1
  • Oxidopamine
  • Dopamine