ArticleThe Journal of biological chemistry2011
Opioid-induced down-regulation of RGS4: role of ubiquitination and implications for receptor cross-talk.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
- Epigenetic mechanisms of HIV and opioid-induced neuropathology: Potential therapies and interventions.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Genetic mouse models in opioid research: current status and future directions.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- Article
- The roles of ubiquitin-proteasome system and regulator of G protein signaling 4 in behavioral sensitization induced by a single morphine exposure.Brain and behavior · 2023Article
- Regulators of G Protein Signaling in Analgesia and Addiction.Molecular pharmacology · 2020Review
- Interplay between the Endogenous Opioid System and Proteasome Complex: Beyond Signaling.International journal of molecular sciences · 2019Review
- RGS4 Overexpression in Lung Attenuates Airway Hyperresponsiveness in Mice.American journal of respiratory cell and molecular biology · 2018Article
- Regulating the regulators: Epigenetic, transcriptional, and post-translational regulation of RGS proteins.Cellular signalling · 2018Review
- The delta opioid receptor tool box.Neuroscience · 2016Review
- Mu opioid receptor activation enhances regulator of G protein signaling 4 association with the mu opioid receptor/G protein complex in a GTP-dependent manner.Journal of neurochemistry · 2015Article
- Dimethyl Fumarate Protects Neural Stem/Progenitor Cells and Neurons from Oxidative Damage through Nrf2-ERK1/2 MAPK Pathway.International journal of molecular sciences · 2015Article
- RGS4 inhibits angiotensin II signaling and macrophage localization during renal reperfusion injury independent of vasospasm.Kidney international · 2015Article
- 5-HT1A receptor-mediated phosphorylation of extracellular signal-regulated kinases (ERK1/2) is modulated by regulator of G protein signaling protein 19.Cellular signalling · 2014Article
- Roles of the ubiquitin proteasome system in the effects of drugs of abuse.Frontiers in molecular neuroscience · 2014Review
- Role of regulator of G protein signaling proteins in bone.Frontiers in bioscience (Landmark edition) · 2014Review
- Rab family proteins regulate the endosomal trafficking and function of RGS4.The Journal of biological chemistry · 2013Article
- Brain RGS4 and RGS10 protein expression in schizophrenia and depression. Effect of drug treatment.Psychopharmacology · 2013Article
- Modulation of μ-opioid receptor signaling by RGS19 in SH-SY5Y cells.Molecular pharmacology · 2013Article
- A finer tuning of G-protein signaling through regulated control of RGS proteins.American journal of physiology. Heart and circulatory physiology · 2012Review
- μ-Opioid receptors and regulators of G protein signaling (RGS) proteins: from a symposium on new concepts in mu-opioid pharmacology.Drug and alcohol dependence · 2012Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Regulator of G protein signaling protein 4 (RGS4) acts as a GTPase accelerating protein to modulate μ- and δ- opioid receptor (MOR and DOR, respectively) signaling. In turn, exposure to MOR agonists leads to changes in RGS4 at the mRNA and/or protein level. Here we have used human neuroblastoma SH-SY5Y cells that endogenously express MOR, DOR, and RGS4 to study opioid-mediated down-regulation of RGS4. Overnight treatment of SH-SY5Y cells with the MOR agonist DAMGO or the DOR agonist DPDPE decreased RGS4 protein by ∼60% accompanied by a profound loss of opioid receptors but with no change in RGS4 mRNA. The decrease in RGS4 protein was prevented by the pretreatment with pertussis toxin or the opioid antagonist naloxone. The agonist-induced down-regulation of RGS4 proteins was completely blocked by treatment with the proteasome inhibitors MG132 or lactacystin or high concentrations of leupeptin, indicating involvement of ubiquitin-proteasome and lysosomal degradation. Polyubiquitinated RGS4 protein was observed in the presence of MG132 or the specific proteasome inhibitor lactacystin and promoted by opioid agonist. The loss of opioid receptors was not prevented by MG132, demonstrating a different degradation pathway. RGS4 is a GTPase accelerating protein for both Gα(i/o) and Gα(q) proteins. After overnight treatment with DAMGO to reduce RGS4 protein, signaling at the Gα(i/o)-coupled DOR and the Gα(q)-coupled M(3) muscarinic receptor (M(3)R) was increased but not signaling of the α(2) adrenergic receptor or bradykinin BK(2) receptor, suggesting the development of cross-talk between the DOR and M(3)R involving RGS4.
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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.