Trafficking of Adenosine A<SUB>2A</SUB> and Dopamine D<SUB>2</SUB> Receptors

Abstract

An interaction between adenosine A2A and dopamine D2 receptors has been demonstrated previously. It is generally found that agonist treatment internalizes receptors, including A2A and D2, whereas less is known of the long-term effects involved in the agonist-mediated trafficking of A2A 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 A2A and D2 agonist and D2 antagonist treatments on both A2A 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 A2A 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 A2A/D2 receptors. These A2A/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 A2A and D2 immunoreactivity, indicating that the D2 antagonist stabilizes the D2 receptor and thereby reduces the internalization of both of the A2A and D2 receptors. Taken together, an activation of either A2A and D2 receptor or blockade of D2 receptors will cause long-lasting changes in A2A and D2 receptor trafficking.

Increased desensitization of dopamine D2 receptor-mediated response in the ventral tegmental area in the absence of adenosine A2A receptors

“…2) (Nimitvilai & Brodie, 2010), showing agonist and concentration-dependency of receptor internalisation. (Ferre et al, 2008) and their heterodimers also have the potential to internalise differentially from each homomers and, thereby, desensitise differentially (Hillion et al, 2002;Torvinen et al, 2005;Vidi et al, 2008). We also show here that the A 2A receptor agonist, CGS21680, did not cause any pharmacological effect on the firing rate or pattern of dopamine neurons, confirming the lack of pharmacologically accessible A 2A receptors on dopamine neurons, which is in agreement with a low level of A 2A receptor expression in the VTA (Rosin et al, 1998;Rosin et al, 2003).…”

Adenosine A2A Receptor and Dopamine D3 Receptor Interactions: Evidence of Functional A2A/D3 Heteromeric Complexes

“…The "multiplyfunction method" allows for the discrimination of the high-intensity/ density clusters of colocalizing fluorophors (Torvinen et al, 2005). The multiply-function method performs the pixel-by-pixel multiplication of the two images and divides (always pixel-by-pixel) the result by a factor (1,. .…”

Identification of Two Functionally Distinct Endosomal Recycling Pathways for Dopamine D2Receptor

“…For this reason, most antipsychotics currently in use are DRD2 antagonists. The function of DRD2 is determined by its levels on the plasma membrane (PM) (Lin et al, 2001Binda et al, 2002;Free et al, 2007;Kim et al, 2008a,b;Tirotta et al, 2008;Genedani et al, 2010), and DRD2 endocytosis plays an important role in its desensitization following DA stimulation (Kim et al, 2001;Jeanneteau et al, 2004;Kabbani et al, 2004;Macey et al, 2004;Namkung and Sibley, 2004;Sugiura et al, 2004;Bartlett et al, 2005;Genedani et al, 2005;Torvinen et al, 2005;Paspalas et al, 2006;Iizuka et al, 2007;Kim, 2008;Xiao et al, 2009;Celver et al, 2010;Shimokawa et al, 2010). However, the fate of DRD2 following DA-induced endocytosis remains controversial.…”