ArticleThe Journal of biological chemistry2005
Mu and kappa opioid receptors activate ERK/MAPK via different protein kinase C isoforms and secondary messengers in astrocytes.
Article in The Journal of biological chemistry, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 174 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
- Sexually-motivated song correlates with opioid- and dopamine-related gene expression in the rostral nucleus accumbens of male European starlings.Behavioural brain research · 2026Article
- Persistent Transcriptome Alterations in Zebrafish Embryos After Discontinued Opioid Exposure.International journal of molecular sciences · 2025Article
- Spatial Mass Cytometry-Based Single-Cell Imaging Reveals a Disrupted Epithelial-Immune Axis in Prurigo Nodularis.The Journal of investigative dermatology · 2024Article
- Decoding the κ Opioid Receptor (KOR): Advancements in Structural Understanding and Implications for Opioid Analgesic Development.Molecules (Basel, Switzerland) · 2024Review
- Opioid Mechanisms and the Treatment of Depression.Current topics in behavioral neurosciences · 2024Review
- Kappa opioid receptor in nucleus accumbens regulates depressive-like behaviors following prolonged morphine withdrawal in mice.iScience · 2023Article
- 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
- Three-Dimensional Structural Insights Have Revealed the Distinct Binding Interactions of Agonists, Partial Agonists, and Antagonists with the µ Opioid Receptor.International journal of molecular sciences · 2023Review
- Synthesis and Antiproliferative Activity against Cancer Cells of Indole-Aryl-Amide Derivatives.Molecules (Basel, Switzerland) · 2022Article
- Morphine-induced changes in the function of microglia and macrophages after acute spinal cord injury.BMC neuroscience · 2022Article
- The opioid system in depression.Neuroscience and biobehavioral reviews · 2022Review
- Amygdala dynorphin/κ opioid receptor system modulates depressive-like behavior in mice following chronic social defeat stress.Acta pharmacologica Sinica · 2022Article
- Differences in dopamine and opioid receptor ratios in the nucleus accumbens relate to physical contact and undirected song in pair-bonded zebra finches.Behavioral neuroscience · 2022Article
- Endogenous Opioid Dynorphin Is a Potential Link between Traumatic Brain Injury, Chronic Pain, and Substance Use Disorder.Journal of neurotrauma · 2022Review
- Mu-opioid receptor and receptor tyrosine kinase crosstalk: Implications in mechanisms of opioid tolerance, reduced analgesia to neuropathic pain, dependence, and reward.Frontiers in systems neuroscience · 2022Review
- Birdsong and the Neural Regulation of Positive Emotion.Frontiers in psychology · 2022Review
- Peptide Kappa Opioid Receptor Ligands and Their Potential for Drug Development.Handbook of experimental pharmacology · 2022Review
- PKCζ-Mitogen-Activated Protein Kinase Signaling Mediates Crotalphine-Induced Antinociception.Toxins · 2021Article
- Kappa opioid receptor modulation of excitatory drive onto nucleus accumbens fast-spiking interneurons.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Acute mu and kappa opioids activate the ERK/MAPK phosphorylation cascade that represents an integral part of the signaling pathway of growth factors in astrocytes. By this cross-talk, opioids may impact neural development and plasticity among other basic neurobiological processes in vivo. The mu agonist, [D-ala2,mephe4,glyol5]enkephalin (DAMGO), induces a transient stimulation of ERK phosphorylation, whereas kappa agonist, U69,593, engenders sustained ERK activation. Here we demonstrate that acute U69,593 and DAMGO stimulate ERK phosphorylation by utilization of different secondary messengers and protein kinase C (PKC) isoforms upstream of the growth factor pathway. Immortalized astrocytes transfected with either antisense calmodulin (CaM), a mutant mu opioid receptor that binds CaM poorly or a dominant negative mutant of PKCepsilon were used as a model system to study mu signaling. Evidence was gained to implicate CaM and PKCepsilon in DAMGO stimulation of ERK. DAMGO activation of PKCepsilon and/or ERK was insensitive to selective inhibitors of Ca2+ mobilization, but it was blocked upon phospholipase C inhibition. These results suggest a novel mechanism wherein, upon DAMGO binding, CaM is released from the mu receptor and activates phospholipase C. Subsequently, phospholipase C generates diacylglycerides that activate PKCepsilon. In contrast, U69,593 appears to act via phosphoinositide 3-kinase, PKCzeta, and Ca2+ mobilization. These signaling components were implicated based on studies with specific inhibitors and a dominant negative mutant of PKCzeta. Collectively, our findings on acute opioid effects suggest that differences in their mechanism of signaling may contribute to the distinct outcomes on ERK modulation induced by chronic mu and kappa opioids.
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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.