Coaggregation, cointernalization, and codesensitization of adenosine A2A receptors and dopamine D2 receptors.
Antagonistic and reciprocal interactions are known to exist between adenosine and dopamine receptors in the striatum. In the present study, double immunofluorescence experiments with confocal laser microscopy showed a high degree of colocalization of adenosine A(2A) receptors (A(2A)R) and dopamine D(2) receptors (D(2)R) in cell membranes of SH-SY5Y human neuroblastoma cells stably transfected with human D(2)R and in cultured striatal cells. A(2A)R/D(2)R heteromeric complexes were demonstrated in coimmunoprecipitation experiments in membrane preparations from D(2)R-transfected SH-SY5Y cells and from mouse fibroblast Ltk(-) cells stably transfected with human D(2)R (long form) and transiently cotransfected with the A(2A)R double-tagged with hemagglutinin. Long term exposure to A(2A)R and D(2)R agonists in D(2)R-cotransfected SH-SY5Y cells resulted in coaggregation, cointernalization and codesensitization of A(2A)R and D(2)R. These results give a molecular basis for adenosine-dopamine antagonism at the membrane level and have implications for treatment of Parkinson's disease and schizophrenia, in which D(2)R are involved.
Hillion
Joelle
J
Department of Neuroscience, Karolinska Institute, 17177 Stockholm, Sweden. hillionj@ninds.nih.gov
Canals
Meritxell
M
Torvinen
Maria
M
Casado
Vicent
V
Scott
Rizaldy
R
Terasmaa
Anton
A
Hansson
Anita
A
Watson
Stanley
S
Olah
Mark E
ME
Mallol
Josefa
J
Canela
Enric I
EI
Zoli
Michele
M
Agnati
Luigi F
LF
Ibanez
Carlos F
CF
Lluis
Carme
C
Franco
Rafael
R
Ferre
Sergi
S
Fuxe
Kjell
K
D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal; D010300:Parkinson Disease / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D043705:Receptor, Adenosine A2A; D017448:Receptors, Dopamine D2; D018047:Receptors, Purinergic P1; D019257:Quinpirole; D000242:Cyclic AMP