ArticleProceedings of the National Academy of Sciences of the United States of America2001
Oligomerization of opioid receptors with beta 2-adrenergic receptors: a role in trafficking and mitogen-activated protein kinase activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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Who cites it
102 citing papers in PubMed, 324 citations in OpenAlex.
- Dynamic monomer-dimer transition in ligand-induced apelin receptor activation.Nature communications · 2026Article
- Local GPCR density tips the balance of μ-opioid receptor trafficking.bioRxiv : the preprint server for biology · 2026Article
- Selection for Molecularly Complementary Modules (MCMs) Drives the Origins and Evolution of Pleiofunctional, Epistatic Interactomes (PEIs).Life (Basel, Switzerland) · 2026Review
- β2-Adrenergic Receptor Utilizes Distinct Interaction Interfaces to Selectively form Heterooligomers with a Subset of Bitter Taste Receptors.Biochemistry · 2025Article
- Monoamine-Uptake Inhibitors and Pain: Antidepressant Drugs Among First-Line Treatments Against Neuropathic Pain and Fibromyalgia.Advances in neurobiology · 2025Review
- Melanocortin-4 Receptor PLC Activation Is Modulated by an Interaction with the Monocarboxylate Transporter 8.International journal of molecular sciences · 2024Article
- Review
- Review
- 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
- 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
- Article
- Interclass GPCR heteromerization affects localization and trafficking.Science signaling · 2020Article
- 2016 Philip S. Portoghese Medicinal Chemistry Lectureship: Designing Bivalent or Bitopic Molecules for G-Protein Coupled Receptors. The Whole Is Greater Than the Sum of Its Parts.Journal of medicinal chemistry · 2020Article
- Mutual Enhancement of Opioid and Adrenergic Receptors by Combinations of Opioids and Adrenergic Ligands Is Reflected in Molecular Complementarity of Ligands: Drug Development Possibilities.International journal of molecular sciences · 2019Article
- Receptor Heterodimerization Modulates Endocytosis through Collaborative and Competitive Mechanisms.Biophysical journal · 2019Article
- Arrestin recruitment and signaling by G protein-coupled receptor heteromers.Neuropharmacology · 2019Review
- Peripheral Delta Opioid Receptors Mediate Formoterol Anti-allodynic Effect in a Mouse Model of Neuropathic Pain.Frontiers in molecular neuroscience · 2019Article
- Oligomerization of MrgC11 and μ-opioid receptors in sensory neurons enhances morphine analgesia.Science signaling · 2018Article
- Adrenergic Agonists Bind to Adrenergic-Receptor-Like Regions of the Mu Opioid Receptor, Enhancing Morphine and Methionine-Enkephalin Binding: A New Approach to "Biased Opioids"?International journal of molecular sciences · 2018Article
42 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
G-protein-coupled receptors (GPCRs) have recently joined the list of cell surface receptors that dimerize. Dimerization has been shown to alter the ligand-binding, signaling, and trafficking properties of these receptors. Recent studies have shown that GPCRs heterodimerize with closely related members, resulting in the modulation of their function. In this study, we have attempted to determine whether members of GPCR superfamilies that couple to different families of G-proteins can associate and form oligomers. We chose the beta2 adrenergic receptor that couples to stimulatory G-proteins and delta & kappa opioid receptors that couple to inhibitory G-proteins. beta2 and delta receptors undergo robust agonist-mediated endocytosis, whereas kappa receptors do not. We find that when coexpressed, beta2 receptors can form heteromeric complexes with both delta and kappa receptors. This heterooligomerization does not significantly alter the ligand binding or coupling properties of the receptors. However, it affects the trafficking properties of the receptors. For example, we find that delta receptors, when coexpressed with beta2 receptors, undergo isoproterenol-mediated endocytosis. Conversely, beta2 receptors in these cells undergo etorphine-mediated endocytosis. However, beta2 receptors, when coexpressed with kappa receptors, undergo neither opioid- nor isoproterenol-mediated endocytosis. Moreover, these cells exhibit a substantial decrease in the isoproterenol-induced phosphorylation of mitogen-activated protein kinases. Taken together, these results provide direct evidence of heteromerization of GPCRs that couple to different types of G-proteins, which results in the modulation of receptor trafficking and signal transduction.
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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.