Ontology type: schema:ScholarlyArticle Open Access: True
2003-02-27
AUTHORSOliver Kudlacek, Herwig Just, Vladimir M Korkhov, Nina Vartian, Markus Klinger, Halyna Pankevych, Qiong Yang, Christian Nanoff, Michael Freissmuth, Stefan Boehm
ABSTRACTThe adenosine A2A receptor and the dopamine D2 receptor are prototypically coupled to Gs and Gi/Go, respectively. In striatal intermediate spiny neurons, these receptors are colocalized in dendritic spines and act as mutual antagonists. This antagonism has been proposed to occur at the level of the receptors or of receptor–G protein coupling. We tested this model in PC12 cells which endogenously express A2A receptors. The human D2 receptor was introduced into PC12 cells by stable transfection. A2A-agonist-mediated inhibition of D2 agonist binding was absent in PC12 cell membranes but present in HEK293 cells transfected as a control. However, in the resulting PC12 cell lines, the action of the D2 agonist quinpirole depended on the expression level of the D2 receptor: at low and high receptor levels, the A2A-agonist-induced elevation of cAMP was enhanced and inhibited, respectively. Forskolin-stimulated cAMP formation was invariably inhibited by quinpirole. The effects of quinpirole were abolished by pretreatment with pertussis toxin. A2A-receptor-mediated cAMP formation was inhibited by other Gi/Go-coupled receptors that were either endogenously present (P2y12-like receptor for ADP) or stably expressed after transfection (A1 adenosine, metabotropic glutamate receptor-7A). Similarly, voltage activated Ca2+ channels were inhibited by the endogenous P2Y receptor and by the heterologously expressed A1 receptor but not by the D2 receptor. These data indicate functional segregation of signaling components. Our observations are thus compatible with the proposed model that D2 and A2A receptors are closely associated, but they highlight the fact that this interaction can also support synergism. More... »
PAGES1317-1327
http://scigraph.springernature.com/pub.10.1038/sj.npp.1300181
DOIhttp://dx.doi.org/10.1038/sj.npp.1300181
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PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/12784121
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