ArticleThe Journal of biological chemistry2009
p38 MAPK and beta-arrestin 2 mediate functional interactions between endogenous micro-opioid and alpha2A-adrenergic receptors in neurons.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 56 citations in OpenAlex.
- Mechanisms of Location Bias in G Protein-Coupled Receptors.Handbook of experimental pharmacology · 2026Review
- Article
- Mu-opioid mediated discriminative stimulus effects of fentanyl and xylazine: Dose-response and time-course studies.Drug and alcohol dependence · 2025Article
- The Mitragyna speciosa (kratom) alkaloid mitragynine: Analysis of adrenergic αEuropean journal of pharmacology · 2024Article
- Non-Peptide Opioids Differ in Effects on Mu-Opioid (MOP) and Serotonin 1A (5-HTMolecules (Basel, Switzerland) · 2022Article
- Interaction of opioid with insulin/IGFs signaling in Alzheimer's disease.Journal of molecular neuroscience : MN · 2020Review
- Mu Opioid Receptor Heterodimers Emerge as Novel Therapeutic Targets: Recent Progress and Future Perspective.Frontiers in pharmacology · 2020Review
- Heteromerization Modulates mu Opioid Receptor Functional PropertiesFrontiers in pharmacology · 2018Review
- Blockade of neuronal dopamine D2 receptor attenuates morphine tolerance in mice spinal cord.Scientific reports · 2016Article
- Impedance-based analysis of mu opioid receptor signaling and underlying mechanisms.Biochemistry and biophysics reports · 2016Article
- Inhibition of GABAergic Neurotransmission by HIV-1 Tat and Opioid Treatment in the Striatum Involves μ-Opioid Receptors.Frontiers in neuroscience · 2016Article
- Dual allosteric modulation of opioid antinociceptive potency by α2A-adrenoceptors.Neuropharmacology · 2015Article
- Analgesic synergy between opioid and α2 -adrenoceptors.British journal of pharmacology · 2015Review
- Effect of acute fentanyl treatment on synaptic plasticity in the hippocampal CA1 region in rats.Frontiers in pharmacology · 2015Article
- Heterologous regulation of Mu-opioid (MOP) receptor mobility in the membrane of SH-SY5Y cells.The Journal of biological chemistry · 2014Article
- Functional characterization of G-protein-coupled receptors: a bioinformatics approach.Neuroscience · 2014Article
- Revolution in GPCR signalling: opioid receptor heteromers as novel therapeutic targets: IUPHAR review 10.British journal of pharmacology · 2014Review
- The Concise Guide to PHARMACOLOGY 2013/14: G protein-coupled receptors.British journal of pharmacology · 2013Article
- Select G-protein-coupled receptors modulate agonist-induced signaling via a ROCK, LIMK, and β-arrestin 1 pathway.Cell reports · 2013Article
- Regulation of μ-opioid receptors: desensitization, phosphorylation, internalization, and tolerance.Pharmacological reviews · 2013Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Formation of receptor complexes between micro-opioid and alpha2A-adrenergic receptors has been demonstrated in transfected cells. The functional significance and underlying mechanisms of such receptor interactions remain to be determined in neuronal systems. We examined functional interactions between endogenous micro and alpha2A receptors in mouse dorsal root ganglion neurons. Acute application of the micro agonist [D-Ala2,N-MePhe4, Gly-ol5]enkephalin (DAMGO) or the alpha2 agonist clonidine inhibited voltage-gated Ca2+ currents in these neurons. Prolonged treatment with either DAMGO or clonidine induced a mutual cross-desensitization between micro and alpha2A receptor-mediated current inhibition. The cross-desensitization was closely associated with simultaneous internalization of micro and alpha2A receptors. Morphine, a mu agonist triggering little mu receptor endocytosis, induced neither cross-desensitization nor internalization of alpha2A receptors. Furthermore, inhibition of p38 MAPK prevented the cross-desensitization as well as cointernalization of micro and alpha2A receptors. Changes in receptor trafficking profiles suggested that p38 MAPK activity was required for initiating micro receptor internalization and maintaining possible micro-alpha2A association during their cointernalization. Finally, the micro-alpha2A cross-desensitization was absent in dorsal root ganglion neurons lacking beta-arrestin 2. These findings demonstrated p38 MAPK- and beta-arrestin 2-dependent cross-regulation between neuronal micro and alpha2A receptors. By promoting receptor cross-desensitization and cointernalization, such functional interactions may serve as negative feedback mechanisms triggered by prolonged agonist exposure to modulate the signaling of functionally related G protein-coupled receptors.
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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.