Premium
D 2L dopamine receptor‐mediated heterologous sensitization of adenylyl cyclase 2 is Gβγ subunit‐dependent
Author(s) -
Conley Jason Michael,
Watts Val
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1011.2
Subject(s) - sensitization , adenylyl cyclase , signal transduction , hek 293 cells , microbiology and biotechnology , chemistry , receptor , g protein , protein subunit , pharmacology , biology , neuroscience , biochemistry , gene
The focus of the present study was to identify components of the signaling pathways underlying the enhanced responsiveness of adenylyl cyclase 2 (AC2) to phorbol ester stimulation following persistent activation of the D 2L dopamine receptor. The heightened sensitivity of adenylyl cyclases following persistent Gi‐coupled receptor activation is known as heterologous sensitization and is thought to be linked to dependence associated with drugs of abuse. Our studies utilized HEK293 cells expressing AC2 and the D 2L dopamine receptor to examine sensitization of AC2. Co‐expression of either the G protein regulator AGS3 or the Gβγ sequestering protein βARKct‐CD8 resulted in a blockade of AC2 sensitization following persistent D 2L receptor activation, suggesting that Gβγ subunits are important mediators of AC2 sensitization. Gβγ subunits modulate a variety of effector proteins that are potentially embedded in the signaling pathways that support AC sensitization. To broadly study these signaling pathways, steps have been taken to explore cAMP biosensor technologies and miniaturize our sensitization experiments to make them amenable for siRNA library screening. Taken together, we have identified Gβγ subunits as components of AC2 sensitization and have devoloped assay formats to identify downstream signaling pathways underlying this adaptive response. Our work was supported by grant MH060397 to VJW.