%0 Journal Article
%T Dopamine  Receptor-Mediated Heterologous Sensitization of AC5 Requires Signalosome Assembly
%A Karin F. K. Ejendal
%A Carmen W. Dessauer
%A Terence E. H¨¦bert
%A Val J. Watts
%J Journal of Signal Transduction
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/210324
%X Chronic dopamine receptor activation is implicated in several central nervous system disorders. Although acute activation of Gi-coupled D2 dopamine receptors inhibits adenylyl cyclase, persistent activation enhances adenylyl cyclase activity, a phenomenon called heterologous sensitization. Previous work revealed a requirement for Gs in D2-induced heterologous sensitization of AC5. To elucidate the mechanism of Gs dependency, we expressed Gs mutants in Gs-deficient E2£¿/E2£¿ cells. Neither Gs-palmitoylation nor Gs-Gβγ interactions were required for sensitization of AC5. Moreover, we found that coexpressing βARKct-CD8 or Sar1(H79G) blocked heterologous sensitization. These studies are consistent with a role for Gs-AC5 interactions in sensitization however, Gβγ appears to have an indirect role in heterologous sensitization of AC5, possibly by promoting proper signalosome assembly.
%U http://www.hindawi.com/journals/jst/2012/210324/