ArticleJournal of neurochemistry2008
Kappa opioids promote the proliferation of astrocytes via Gbetagamma and beta-arrestin 2-dependent MAPK-mediated pathways.
Article in Journal of neurochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
56 citing papers in PubMed, 90 citations in OpenAlex.
- Astroglial kappa opioid receptor-mediated reduction of glutamate exchanger xCT in the prelimbic cortex underlies chronic stress-induced depressive-like behaviors.Molecular psychiatry · 2026Article
- κ-Opioid Receptor Agonists as Robust Pain-Modulating Agents: Mechanisms and Therapeutic Potential in Pain Modulation.Journal of clinical medicine · 2025Review
- κ-opioid receptor: from analgesic target to neuroimmune hub.Frontiers in pharmacology · 2025Review
- Limitations and potential of κOR biased agonists for pain and itch management.Neuropharmacology · 2024Review
- Ketamine and Major Ketamine Metabolites Function as Allosteric Modulators of Opioid Receptors.Molecular pharmacology · 2024Article
- The Kappa Opioid Receptor Agonist 16-Bromo Salvinorin A Has Anti-Cocaine Effects without Significant Effects on Locomotion, Food Reward, Learning and Memory, or Anxiety and Depressive-like Behaviors.Molecules (Basel, Switzerland) · 2023Article
- Bedside to bench: the outlook for psychedelic research.Frontiers in pharmacology · 2023Review
- Biased Ligands at the Kappa Opioid Receptor: Fine-Tuning Receptor Pharmacology.Handbook of experimental pharmacology · 2022Review
- Peptide Kappa Opioid Receptor Ligands and Their Potential for Drug Development.Handbook of experimental pharmacology · 2022Review
- Fundamentals of the Dynorphins/Kappa Opioid Receptor System: From Distribution to Signaling and Function.Handbook of experimental pharmacology · 2022Article
- Reactive Astrocytes: Critical Players in the Development of Chronic Pain.Frontiers in psychiatry · 2021Review
- The Role of the Kappa Opioid System in Comorbid Pain and Psychiatric Disorders: Function and Implications.Frontiers in neuroscience · 2021Review
- Opioid and neuroHIV Comorbidity - Current and Future Perspectives.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020Review
- Interaction of opioid with insulin/IGFs signaling in Alzheimer's disease.Journal of molecular neuroscience : MN · 2020Review
- Role of Astrocytic Dysfunction in the Pathogenesis of Parkinson's Disease Animal Models from a Molecular Signaling Perspective.Neural plasticity · 2020Review
- Functional Selectivity and Antinociceptive Effects of a Novel KOPr Agonist.Frontiers in pharmacology · 2020Article
- Turning the 'Tides on Neuropsychiatric Diseases: The Role of Peptides in the Prefrontal Cortex.Frontiers in behavioral neuroscience · 2020Article
- Reactive oxygen species (ROS) generation is stimulated by κ opioid receptor activation through phosphorylated c-Jun N-terminal kinase and inhibited by p38 mitogen-activated protein kinase (MAPK) activation.The Journal of biological chemistry · 2019Article
- The Natural Compound Climacostol as a Prodrug Strategy Based on pH Activation for Efficient Delivery of Cytotoxic Small Agents.Frontiers in chemistry · 2019Article
- Structurally Related Kappa Opioid Receptor Agonists with Substantial Differential Signaling Bias: Neuroendocrine and Behavioral Effects in C57BL6 Mice.The international journal of neuropsychopharmacology · 2018Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
GTP binding regulatory protein (G protein)-coupled receptors can activate MAPK pathways via G protein-dependent and -independent mechanisms. However, the physiological outcomes correlated with the cellular signaling events are not as well characterized. In this study, we examine the involvement of G protein and beta-arrestin 2 pathways in kappa opioid receptor-induced, extracellular signal-regulated kinase 1/2 (ERK1/2)-mediated proliferation of both immortalized and primary astrocyte cultures. As different agonists induce different cellular signaling pathways, we tested the prototypic kappa agonist, U69593 as well as the structurally distinct, non-nitrogenous agonist, C(2)-methoxymethyl salvinorin B (MOM-Sal-B). In immortalized astrocytes, U69593, activated ERK1/2 by a rapid (min) initial stimulation that was sustained over 2 h and increased proliferation. Sequestration of activated Gbetagamma subunits attenuated U69593 stimulation of ERK1/2 and suppressed proliferation in these cells. Furthermore, small interfering RNA silencing of beta-arrestin 2 diminished sustained ERK activation induced by U69593. In contrast, MOM-Sal-B induced only the early phase of ERK1/2 phosphorylation and did not affect proliferation of immortalized astrocytes. In primary astrocytes, U69593 produced the same effects as seen in immortalized astrocytes. MOM-Sal-B elicited sustained ERK1/2 activation which was correlated with increased primary astrocyte proliferation. Proliferative actions of both agonists were abolished by either inhibition of ERK1/2, Gbetagamma subunits or beta-arrestin 2, suggesting that both G protein-dependent and -independent ERK pathways are required for this outcome.
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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.