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AGS3 blocks D2L dopamine receptor‐mediated heterologous sensitization of adenylyl cyclase 2
Author(s) -
Conley Jason Michael,
Watts Val J
Publication year - 2010
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.24.1_supplement.587.5
Subject(s) - adenylyl cyclase , receptor , heterologous , sensitization , g protein , activator (genetics) , signal transduction , microbiology and biotechnology , g protein coupled receptor , biology , chemistry , medicine , endocrinology , biochemistry , immunology , gene
The present study was designed to investigate the function of the activator of G protein‐signaling 3 (AGS3/Gpsm1) in cellular signaling. AGS3 acts in vitro as a guanine nucleotide dissociation inhibitor by binding Gαi in the GDP‐bound state and has been implicated in drug‐seeking or relapse behavior in rats dependent on cocaine, ethanol, or heroin. HEK293 cells expressing adenylyl cyclase type 2 (AC2) and the D 2L dopamine receptor were utilized to study the effects of AGS3 expression on G protein signaling following acute or persistent activation of the D 2L receptor. AGS3 produced no discernable changes in Gβγ‐dependent stimulation of AC2 upon acute D 2L receptor activation. Similar studies revealed analogous results when acute D 2L ‐stimulated ERK1/2 activation was examined in the presence or absence of AGS3. Subsequent experiments revealed that AGS3 lacked effects on long‐term D 2L receptor desensitization. In contrast, the expression of AGS3 completely blocked D 2L receptor‐mediated heterologous sensitization. These findings suggest that desensitization and heterologous sensitization depend on distinct mechanisms and that AGS3 may play a role in regulation of D 2L receptor‐mediated heterologous sensitization. Our results are consistent with the work of Bohn and colleagues, who showed that tolerance and dependence involve distinct signaling pathways. This work was supported by grant MH060397 to VJW.