title: Dopamine D(2) Receptor-Mediated Heterologous Sensitization of AC5 Requires Signalosome Assembly.
abstract: Chronic dopamine receptor activation is implicated in several central nervous system disorders. Although acute activation of Gα(i)-coupled D(2) dopamine receptors inhibits adenylyl cyclase, persistent activation enhances adenylyl cyclase activity, a phenomenon called heterologous sensitization. Previous work revealed a requirement for Gα(s) in D(2)-induced heterologous sensitization of AC5. To elucidate the mechanism of Gα(s) dependency, we expressed Gα(s) mutants in Gα(s)-deficient Gnas(E2-/E2-) cells. Neither Gα(s)-palmitoylation nor Gα(s)-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 Gα(s)-AC5 interactions in sensitization however, Gβγ appears to have an indirect role in heterologous sensitization of AC5, possibly by promoting proper signalosome assembly.
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907-2051, USA.
authors.forename: Karin F K
authors.initials: KF
authors.lastname: Ejendal
authors.forename: Carmen W
authors.initials: CW
authors.lastname: Dessauer
authors.forename: Terence E
authors.initials: TE
authors.lastname: Hébert
authors.forename: Val J
authors.initials: VJ
authors.lastname: Watts