ArticleScientific reports2015
Structural and functional interactions between six-transmembrane μ-opioid receptors and β2-adrenoreceptors modulate opioid signaling.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 38 citations in OpenAlex.
- Intracellular cAMP Signaling Pathway via GBiomedicines · 2023Article
- Beta 2 adrenergic receptor and mu opioid receptor interact to potentiate the aggressiveness of human breast cancer cell by activating the glycogen synthase kinase 3 signaling.Breast cancer research : BCR · 2022Article
- Exploring Pharmacological Functions of Alternatively Spliced Variants of the Mu Opioid Receptor Gene,International journal of molecular sciences · 2022Review
- Biased, Bitopic, Opioid-Adrenergic Tethered Compounds May Improve Specificity, Lower Dosage and Enhance Agonist or Antagonist Function with Reduced Risk of Tolerance and Addiction.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Co-Evolution of Opioid and Adrenergic Ligands and Receptors: Shared, Complementary Modules Explain Evolution of Functional Interactions and Suggest Novel Engineering Possibilities.Life (Basel, Switzerland) · 2021Article
- Alternative Pre-mRNA Splicing of the Mu Opioid Receptor Gene,Biomolecules · 2021Review
- Alternative Splicing of Opioid Receptor Genes Shows a Conserved Pattern for 6TM Receptor Variants.Cellular and molecular neurobiology · 2021Article
- Identification and characterization of novel candidate compounds targeting 6- and 7-transmembrane μ-opioid receptor isoforms.British journal of pharmacology · 2021Article
- Opioid and neuroHIV Comorbidity - Current and Future Perspectives.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020Review
- Targeting the endothelin axis as a therapeutic strategy for oral cancer metastasis and pain.Scientific reports · 2020Article
- A Truncated Six Transmembrane Splice Variant MOR-1G Enhances Expression of the Full-Length Seven TransmembraneMolecular pharmacology · 2020Article
- Stabilization of μ-opioid receptor facilitates its cellular translocation and signaling.Proteins · 2019Article
- Article
- Alternative Splicing of the Delta-Opioid Receptor Gene Suggests Existence of New Functional Isoforms.Molecular neurobiology · 2019Article
- Beta2-Adrenergic Receptor Polymorphisms and Haplotypes Associate With Chronic Pain in Sickle Cell Disease.Frontiers in pharmacology · 2019Article
- Endogenous and Exogenous Opioids in Pain.Annual review of neuroscience · 2018Review
- Advances in Achieving Opioid Analgesia Without Side Effects.Frontiers in pharmacology · 2018Review
- Morphine-induced hyperalgesia involves mu opioid receptors and the metabolite morphine-3-glucuronide.Scientific reports · 2017Article
- Genetic dissociation of morphine analgesia from hyperalgesia in mice.Psychopharmacology · 2017Article
- β-Adrenergic receptor gene expression in HIV-associated neurocognitive impairment and encephalitis: implications for MOR-1K subcellular localization.Journal of neurovirology · 2016Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
The primary molecular target for clinically used opioids is the μ-opioid receptor (MOR). Besides the major seven-transmembrane (7TM) receptors, the MOR gene codes for alternatively spliced six-transmembrane (6TM) isoforms, the biological and clinical significance of which remains unclear. Here, we show that the otherwise exclusively intracellular localized 6TM-MOR translocates to the plasma membrane upon coexpression with β2-adrenergic receptors (β2-ARs) through an interaction with the fifth and sixth helices of β2-AR. Coexpression of the two receptors in BE(2)-C neuroblastoma cells potentiates calcium responses to a 6TM-MOR ligand, and this calcium response is completely blocked by a selective β2-antagonist in BE(2)-C cells, and in trigeminal and dorsal root ganglia. Co-administration of 6TM-MOR and β2-AR ligands leads to substantial analgesic synergy and completely reverses opioid-induced hyperalgesia in rodent behavioral models. Together, our results provide evidence that the heterodimerization of 6TM-MOR with β2-AR underlies a molecular mechanism for 6TM cellular signaling, presenting a unique functional responses to opioids. This signaling pathway may contribute to the hyperalgesic effects of opioids that can be efficiently blocked by β2-AR antagonists, providing a new avenue for opioid therapy.
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