Trafficking of adenosine A_2A and dopamine D₂ receptors

Authors: Torvinen, Maria¹; Torri, Carla²; Tombesi, Andrea²; Marcellino, Daniel³; Watson, Stan⁴; Lluis, Carmen³; Franco, Rafael³; Fuxe, Kjell¹; Agnati, Luigi⁵

Source: Journal of Molecular Neuroscience, Volume 25, Number 2, June 2005 , pp. 191-200(10)

Publisher: Humana Press

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Abstract:

An interaction between adenosine A_2A and dopamine D₂ receptors has been demonstrated previously. It is generally found that agonist treatment internalizes receptors, including A_2A and D₂, whereas less is known of the long-term effects involved in the agonist-mediated trafficking of A_2A and D₂ receptors. Furthermore, the possible influence of the antagonists on receptor trafficking is still undefined. The present studies focus on the long-term effects of A_2A and D₂ agonist and D₂ antagonist treatments on both A_2A and D₂ receptor trafficking studied at three different time intervals—3, 15, and 24 h. In addition, with the fluorescence resonance energy transfer technique, formation of heteromeric A_2A and D₂ receptor complexes was shown in the cotransfected CHO cell line. Confocal microscopy analysis showed that a 3-h treatment with the D₂ agonist induced coaggregation of A_2A/D₂ receptors. These A_2A/D₂ receptor coaggregates internalized after 15 h with a recruitment of the receptors back to the cell membrane after 24 h. In contrast to the effects of the agonist treatment, a 3-h treatment with the D₂-like antagonist raclopride increased both A_2A and D₂ immunoreactivity, indicating that the D₂ antagonist stabilizes the D₂ receptor and thereby reduces the internalization of both of the A_2A and D₂ receptors. Taken together, an activation of either A_2A and D₂ receptor or blockade of D₂ receptors will cause long-lasting changes in A_2A and D₂ receptor trafficking.

Keywords: Adenosine; dopamine; CHO cell line; long-term effects; heterodimer; trafficking; antagonist

Document Type: Research article

DOI: http://dx.doi.org/10.1385/JMN:25:2:191

Affiliations: 1: Department of Neuroscience, Karolinska Institute, 17 177, Stockholm, Sweden, 2: Department of Biomedical Sciences, University of Modena, 41100, Modena, Italy, 3: Department of Biochemistry and Molecular Biology, University of Barcelona, 08028, Barcelona, Spain, 4: Mental Health Institute, University of Michigan, 48109, Ann Arbor, Michigan, 5: Department of Biomedical Sciences, University of Modena, 41100, Modena, Italy, Email: luigiagnati@tin.it

Publication date: 2005-06-01