Differential effects of AGS3 expression on D(2L) dopamine receptor-mediated adenylyl cyclase signaling.

ABSTRACT: Activator of G protein signaling 3 (AGS3) binds G?(i) subunits in the GDP-bound state, implicating AGS3 as an important regulator of G?(i)-linked receptor (e.g., D2 dopamine and ?-opioid) signaling. We examined the ability of AGS3 to modulate recombinant adenylyl cyclase (AC) type 1 and 2 signaling in HEK293 cells following both acute and persistent activation of the D(2L) dopamine receptor (D(2L)DR). AGS3 expression modestly enhanced the potency of acute quinpirole-induced D(2L)DR modulation of AC1 or AC2 activity. AGS3 also promoted desensitization of D(2L)DR-mediated inhibition of AC1, whereas desensitization of D(2L)DR-mediated AC2 activation was significantly attenuated. Additionally, AGS3 reduced D(2L)DR-mediated sensitization of AC1 and AC2. These data suggest that AGS3 is involved in altering G protein signaling in a complex fashion that is effector-specific and dependent on the duration of receptor activation.

SUBMITTER: Conley JM 

PROVIDER: S-EPMC3628818 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature