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

Cell Mol Neurobiol. 2013 May;33(4):551-8. doi: 10.1007/s10571-013-9925-8. Epub 2013 Mar 17.


Activator of G protein signaling 3 (AGS3) binds Gα(i) subunits in the GDP-bound state, implicating AGS3 as an important regulator of Gα(i)-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 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenylyl Cyclases / metabolism*
  • Animals
  • Carrier Proteins / metabolism*
  • HEK293 Cells
  • Humans
  • Illicit Drugs / pharmacology
  • Isoenzymes / metabolism
  • Rats
  • Receptors, Dopamine D2 / metabolism*
  • Signal Transduction* / drug effects


  • Carrier Proteins
  • Gpsm1 protein, rat
  • Illicit Drugs
  • Isoenzymes
  • Receptors, Dopamine D2
  • dopamine D2L receptor
  • Adenylyl Cyclases