Differential Effects of AGS3 Expression on D2L Dopamine Receptor-Mediated Adenylyl Cyclase Signaling |
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Authors: | Jason M. Conley Val J. Watts |
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Affiliation: | 1. Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN, 47907, USA
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Abstract: | Activator of G protein signaling 3 (AGS3) binds Gαi subunits in the GDP-bound state, implicating AGS3 as an important regulator of Gαi-linked receptor (e.g., D2 dopamine and μ-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 D2L dopamine receptor (D2LDR). AGS3 expression modestly enhanced the potency of acute quinpirole-induced D2LDR modulation of AC1 or AC2 activity. AGS3 also promoted desensitization of D2LDR-mediated inhibition of AC1, whereas desensitization of D2LDR-mediated AC2 activation was significantly attenuated. Additionally, AGS3 reduced D2LDR-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. |
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