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Differential Effects of AGS3 Expression on D2L Dopamine Receptor-Mediated Adenylyl Cyclase Signaling

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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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Acknowledgments

We thank Elisabeth Garland and Dr. Karin Ejendal for valuable comments regarding manuscript preparation and Monica Soto Velasquez and Tarsis Brust Fernandes for assistance with confocal microscopy and receptor saturation binding, respectively. We also thank Dr. Stephen Lanier and Dr. Joe Blumer for AGS3 constructs. This work was supported by NIMH Grant MH060397 to VJW.

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  1. Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN, 47907, USA

    Jason M. Conley & Val J. Watts

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  1. Jason M. Conley
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Correspondence to Val J. Watts.

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Conley, J.M., Watts, V.J. Differential Effects of AGS3 Expression on D2L Dopamine Receptor-Mediated Adenylyl Cyclase Signaling. Cell Mol Neurobiol 33, 551–558 (2013). https://doi.org/10.1007/s10571-013-9925-8

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