title: Differential effects of AGS3 expression on D(2L) dopamine receptor-mediated adenylyl cyclase signaling.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Conley
authors.forename: Val J
authors.initials: VJ
authors.lastname: Watts
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D013287:Illicit Drugs / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002352:Carrier Proteins; C498913:Gpsm1 protein, rat; D013287:Illicit Drugs; D007527:Isoenzymes; D017448:Receptors, Dopamine D2; C113776:dopamine D2L receptor; D000262:Adenylyl Cyclases