Trafficking of adenosine A2A and dopamine D2 receptors.
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.
Torvinen
Maria
M
Department of Neuroscience, Karolinska Institute, 17 177 Stockholm, Sweden.
Torri
Carla
C
Tombesi
Andrea
A
Marcellino
Daniel
D
Watson
Stan
S
Lluis
Carmen
C
Franco
Rafael
R
Fuxe
Kjell
K
Agnati
Luigi F
LF
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D004285:Dogs; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D031541:Fluorescence Resonance Energy Transfer; D005455:Fluorescent Antibody Technique; D006801:Humans; D010627:Phenethylamines / Q000494:pharmacology; D021381:Protein Transport / Q000502:physiology*; D019257:Quinpirole / Q000494:pharmacology; D020891:Raclopride / Q000494:pharmacology; D043705:Receptor, Adenosine A2A / Q000235:genetics / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D000959:Antihypertensive Agents; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D010627:Phenethylamines; D043705:Receptor, Adenosine A2A; D017448:Receptors, Dopamine D2; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D019257:Quinpirole; D020891:Raclopride; D000241:Adenosine