ArticleProceedings of the National Academy of Sciences of the United States of America2005
Activator of G protein signaling 3 regulates opiate activation of protein kinase A signaling and relapse of heroin-seeking behavior.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
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Who cites it
50 citing papers in PubMed, 90 citations in OpenAlex.
- The neural circuits and signalling pathways of opioid use disorder.Nature reviews. Neuroscience · 2025Review
- AGS3-based optogenetic GDI induces GPCR-independent Gβγ signalling and macrophage migration.Open biology · 2025Article
- AGS3-based optogenetic GDI induces GPCR-independent Gβγ signaling and macrophage migration.bioRxiv : the preprint server for biology · 2024Article
- GPSM1 impairs metabolic homeostasis by controlling a pro-inflammatory pathway in macrophages.Nature communications · 2022Article
- Intersection of two key signal integrators in the cell: activator of G-protein signaling 3 and dishevelled-2.Journal of cell science · 2020Article
- The Opioid-Addicted Tetrapartite Synapse.Biological psychiatry · 2020Review
- Opioid and Psychostimulant Plasticity: Targeting Overlap in Nucleus Accumbens Glutamate Signaling.Trends in pharmacological sciences · 2018Review
- MicroRNA expression signature of methamphetamine use and addiction in the rat nucleus accumbens.Metabolic brain disease · 2017Article
- Regulation of Chemokine Signal Integration by Activator of G-Protein Signaling 4 (AGS4).The Journal of pharmacology and experimental therapeutics · 2017Article
- The good and bad news about glutamate in drug addiction.Journal of psychopharmacology (Oxford, England) · 2016Review
- Signals from the Fourth Dimension Regulate Drug Relapse.Trends in neurosciences · 2016Review
- The Nucleus Accumbens: Mechanisms of Addiction across Drug Classes Reflect the Importance of Glutamate Homeostasis.Pharmacological reviews · 2016Review
- Activator of G-Protein Signaling 3-Induced Lysosomal Biogenesis Limits Macrophage Intracellular Bacterial Infection.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- S-Glutathionylation and Redox Protein Signaling in Drug Addiction.Progress in molecular biology and translational science · 2016Article
- Activator of G-protein Signaling 3 Controls Renal Epithelial Cell Survival and ERK5 Activation.Journal of molecular signaling · 2015Article
- Direct Coupling of a Seven-Transmembrane-Span Receptor to a Gαi G-Protein Regulatory Motif Complex.Molecular pharmacology · 2015Article
- Astrocytic dysfunction and addiction: consequences of impaired glutamate homeostasis.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2014Review
- Defective chemokine signal integration in leukocytes lacking activator of G protein signaling 3 (AGS3).The Journal of biological chemistry · 2014Article
- Activators of G protein signaling exhibit broad functionality and define a distinct core signaling triad.Molecular pharmacology · 2014Review
- Rapid, transient synaptic plasticity in addiction.Neuropharmacology · 2014Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The nucleus accumbens (NAc) is central to heroin addiction. Activation of opiate receptors in the NAc dissociates G(i/o) into alpha and betagamma subunits. Galpha(i) inhibits cAMP production, but betagamma regulates several molecular pathways, including protein kinase A (PKA). We show in NAc/striatal neurons that opiates paradoxically activate PKA signaling by means of betagamma dimers. Activation requires Galpha(i3) and an activator of G protein signaling 3 (AGS3). AGS3 competes with betagamma for binding to Galpha(i3)-GDP and enhances the action of unbound betagamma. AGS3 and Galpha(i3) knockdown prevents opiate activation of PKA signaling. In rats self-administering heroin, AGS3 antisense in the NAc core, but not shell, eliminates reinstatement of heroin-seeking behavior, a model of human relapse. Thus, Galpha(i3)/betagamma/AGS3 appears to mediate mu opiate receptor activation of PKA signaling as well as heroin-seeking behavior.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.