ArticleMolecular pharmacology2009
Up-regulation of AGS3 during morphine withdrawal promotes cAMP superactivation via adenylyl cyclase 5 and 7 in rat nucleus accumbens/striatal neurons.
Article in Molecular pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 61 citations in OpenAlex.
- Article
- The neural circuits and signalling pathways of opioid use disorder.Nature reviews. Neuroscience · 2025Review
- The influence of morphine treatment on the opioid propeptide gene expression in the forebrain of two inbred mouse strains with different sensitivity to opioids.Pharmacological reports : PR · 2025Article
- Molecular insights into AGS3's role in spindle orientation: a biochemical perspective.Journal of molecular cell biology · 2025Article
- A human iPSC-derived midbrain neural stem cell model of prenatal opioid exposure and withdrawal: A proof of concept study.PloS one · 2025Article
- Transcriptome Analysis of Myocardial Ischemic-Hypoxic Injury in Rats and Hypoxic H9C2 Cells.ESC heart failure · 2024Article
- Opioid system and related ligands: from the past to future perspectives.Journal of anesthesia, analgesia and critical care · 2024Review
- Liquid Biopsy at the Frontier of Kidney Diseases: Application of Exosomes in Diagnostics and Therapeutics.Genes · 2023Review
- Intersection of two key signal integrators in the cell: activator of G-protein signaling 3 and dishevelled-2.Journal of cell science · 2020Article
- Allostatic Changes in the cAMP System Drive Opioid-Induced Adaptation in Striatal Dopamine Signaling.Cell reports · 2019Article
- Modulation of miR-139-5p on chronic morphine-induced, naloxone-precipitated cAMP overshoot in vitro.Metabolic brain disease · 2018Article
- Urinary exosomal expression of activator of G protein signaling 3 in polycystic kidney disease.BMC research notes · 2018Article
- International Union of Basic and Clinical Pharmacology. CI. Structures and Small Molecule Modulators of Mammalian Adenylyl Cyclases.Pharmacological reviews · 2017Review
- Protein Kinase C Epsilon Activity in the Nucleus Accumbens and Central Nucleus of the Amygdala Mediates Binge Alcohol Consumption.Biological psychiatry · 2016Article
- Activator of G-Protein Signaling 3-Induced Lysosomal Biogenesis Limits Macrophage Intracellular Bacterial Infection.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Chronic cocaine disrupts mesocortical learning mechanisms.Brain research · 2015Review
- Phosphorylation of the N-methyl-d-aspartate receptor is increased in the nucleus accumbens during both acute and extended morphine withdrawal.The Journal of pharmacology and experimental therapeutics · 2015Article
- Activator of G-protein Signaling 3 Controls Renal Epithelial Cell Survival and ERK5 Activation.Journal of molecular signaling · 2015Article
- Gα(i/o)-coupled receptor-mediated sensitization of adenylyl cyclase: 40 years later.European journal of pharmacology · 2015Review
- Activators of G protein signaling in the kidney.The Journal of pharmacology and experimental therapeutics · 2015Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Effective medical treatment of opiate addiction is limited by a high relapse rate in abstinent addicts. Opiate withdrawal causes cAMP superactivation, but the underlying molecular mechanisms are not clear. Recent evidence implicates an activator of G-protein signaling 3 (AGS3) in opiate addiction. We found previously that during a 10-min activation of opioid receptors, AGS3 binds G alpha(i)-GDP to promote free G betagamma stimulation of adenylyl cyclase (AC) 2 and 4, and/or inactivate G alpha(i) inhibitory function, thereby transiently enhancing cAMP-dependent protein kinase A (PKA) activity. In contrast, we report here that in nucleus accumbens/striatal neurons, morphine withdrawal induces cAMP superactivation, which requires up-regulation of AGS3. cAMP increases as a function of withdrawal time, by approximately 20% at 10 min and 75% at 5 h. However, cAMP superactivation does not require G betagamma. Instead, adenosine A2A receptor activation of G alpha(s/olf) seems to initiate cAMP superactivation and promote AGS3 up-regulation. Elevated AGS3 binds to G alpha(i) to prevent its inhibition on AC activation. Moreover, withdrawal-induced increases in cAMP/PKA activate phospholipase C and epsilon protein kinase C to further stimulate AC5 and AC7, causing cAMP superactivation. Our findings identify a critical role for AC 5 and 7 and A2A receptors for up-regulation of AGS3 in morphine withdrawal-induced cAMP superactivation.
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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.