Coaggregation, cointernalization, and codesensitization of adenosine A2A receptors and dopamine D2 receptors

Joëlle Hillion*, Meritxell Canals, Maria Torvinen, Vicent Casadó, Rizaldy Scott, Anton Terasmaa, Anita Hansson, Stanley Watson, Mark E. Olah, Josefa Mallol, Enric I. Canela, Michele Zoli, Luigi F. Agnati, Carlos F. Ibáñez, Carme Lluis, Rafael Franco, Sergi Ferré, Kjell Fuxe

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

420 Scopus citations

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 A2A receptors (A2AR) and dopamine D2 receptors (D2R) in cell membranes of SH-SY5Y human neuroblastoma cells stably transfected with human D2R and in cultured striatal cells. A2AR/D2R heteromeric complexes were demonstrated in coimmunoprecipitation experiments in membrane preparations from D2R-transfected SH-SY5Y cells, and from mouse fibroblast Ltk- cells stably transfected with human D2R (long form) and transiently cotransfected with the A2AR double-tagged with hemagglutinin. Long term exposure to A2AR and D2R agonists in D2R-cotransfected SH-SY5Y cells resulted in coaggregation, cointernalization and codesensitization of A2AR and D2R. 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 D2R are involved.

Original languageEnglish (US)
Pages (from-to)18091-18097
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number20
DOIs
StatePublished - May 17 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Coaggregation, cointernalization, and codesensitization of adenosine A<sub>2A</sub> receptors and dopamine D<sub>2</sub> receptors'. Together they form a unique fingerprint.

Cite this