title: Coaggregation, cointernalization, and codesensitization of adenosine A2A receptors and dopamine D2 receptors.
abstract: 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.
authors.affiliation: Department of Neuroscience, Karolinska Institute, 17177 Stockholm, Sweden. hillionj@ninds.nih.gov
authors.forename: Joelle
authors.initials: J
authors.lastname: Hillion
authors.forename: Meritxell
authors.initials: M
authors.lastname: Canals
authors.forename: Maria
authors.initials: M
authors.lastname: Torvinen
authors.forename: Vicent
authors.initials: V
authors.lastname: Casado
authors.forename: Rizaldy
authors.initials: R
authors.lastname: Scott
authors.forename: Anton
authors.initials: A
authors.lastname: Terasmaa
authors.forename: Anita
authors.initials: A
authors.lastname: Hansson
authors.forename: Stanley
authors.initials: S
authors.lastname: Watson
authors.forename: Mark E
authors.initials: ME
authors.lastname: Olah
authors.forename: Josefa
authors.initials: J
authors.lastname: Mallol
authors.forename: Enric I
authors.initials: EI
authors.lastname: Canela
authors.forename: Michele
authors.initials: M
authors.lastname: Zoli
authors.forename: Luigi F
authors.initials: LF
authors.lastname: Agnati
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Ibanez
authors.forename: Carme
authors.initials: C
authors.lastname: Lluis
authors.forename: Rafael
authors.initials: R
authors.lastname: Franco
authors.forename: Sergi
authors.initials: S
authors.lastname: Ferre
authors.forename: Kjell
authors.initials: K
authors.lastname: Fuxe
mesh_terms: 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
chemical_list: D043705:Receptor, Adenosine A2A; D017448:Receptors, Dopamine D2; D018047:Receptors, Purinergic P1; D019257:Quinpirole; D000242:Cyclic AMP