ArticleCellular and molecular life sciences : CMLS2014
Ligand- and cell-dependent determinants of internalization and cAMP modulation by delta opioid receptor (DOR) agonists.
Article in Cellular and molecular life sciences : CMLS, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 42 citations in OpenAlex.
- Divergence in μ and δ opioid receptor pharmacology in neurons and antinociceptive efficacy in neuropathic pain: Insights from MP135 and CYM51010.British journal of pharmacology · 2026Article
- Dipyanone, a new methadone-like synthetic opioid: In vitro and in vivo human metabolism and pharmacological profiling.Archives of toxicology · 2025Article
- Opioid receptors signaling network.Journal of cell communication and signaling · 2022Article
- Comprehensive Signaling Profiles Reveal Unsuspected Functional Selectivity of δ-Opioid Receptor Agonists and Allow the Identification of Ligands with the Greatest Potential for Inducing Cyclase Superactivation.ACS pharmacology & translational science · 2021Article
- Comprehensive overview of biased pharmacology at the opioid receptors: biased ligands and bias factors.RSC medicinal chemistry · 2021Review
- Heteromerization of Endogenous Mu and Delta Opioid Receptors Induces Ligand-Selective Co-Targeting to Lysosomes.Molecules (Basel, Switzerland) · 2020Article
- Agonist-induced phosphorylation bar code and differential post-activation signaling of the delta opioid receptor revealed by phosphosite-specific antibodies.Scientific reports · 2020Article
- Ligand-specific recycling profiles determine distinct potential for chronic analgesic tolerance of delta-opioid receptor (DOPr) agonists.Journal of cellular and molecular medicine · 2020Article
- Vitamin D and Its Potential Interplay With Pain Signaling Pathways.Frontiers in immunology · 2020Review
- Exploring use of unsupervised clustering to associate signaling profiles of GPCR ligands to clinical response.Nature communications · 2019Article
- The δ-opioid receptor positive allosteric modulator BMS 986187 is a G-protein-biased allosteric agonist.British journal of pharmacology · 2019Article
- Tolerance to high-internalizing δ opioid receptor agonist is critically mediated by arrestin 2.British journal of pharmacology · 2018Article
- The role of regulator of G protein signaling 4 in delta-opioid receptor-mediated behaviors.Psychopharmacology · 2017Article
- The delta opioid receptor tool box.Neuroscience · 2016Review
- Molecular Pharmacology of δ-Opioid Receptors.Pharmacological reviews · 2016Review
- Agonist-Specific Recruitment of Arrestin Isoforms Differentially Modify Delta Opioid Receptor Function.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Kir3 channels undergo arrestin-dependant internalization following delta opioid receptor activation.Cellular and molecular life sciences : CMLS · 2015Article
- Cellular signalling of non-synonymous single-nucleotide polymorphisms of the human μ-opioid receptor (OPRM1).British journal of pharmacology · 2015Review
- A Broad G Protein-Coupled Receptor Internalization Assay that Combines SNAP-Tag Labeling, Diffusion-Enhanced Resonance Energy Transfer, and a Highly Emissive Terbium Cryptate.Frontiers in endocrinology · 2015Article
- Identifying ligand-specific signalling within biased responses: focus on δ opioid receptor ligands.British journal of pharmacology · 2015Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Signaling bias refers to G protein-coupled receptor ligand ability to preferentially activate one type of signal over another. Bias to evoke signaling as opposed to sequestration has been proposed as a predictor of opioid ligand potential for generating tolerance. Here we measured whether delta opioid receptor agonists preferentially inhibited cyclase activity over internalization in HEK cells. Efficacy (τ) and affinity (KA) values were estimated from functional data and bias was calculated from efficiency coefficients (log τ/KA). This approach better represented the data as compared to alternative methods that estimate bias exclusively from τ values. Log (τ/KA) coefficients indicated that SNC-80 and UFP-512 promoted cyclase inhibition more efficiently than DOR internalization as compared to DPDPE (bias factor for SNC-80: 50 and for UFP-512: 132). Molecular determinants of internalization were different in HEK293 cells and neurons with βarrs contributing to internalization in both cell types, while PKC and GRK2 activities were only involved in neurons. Rank orders of ligand ability to engage different internalization mechanisms in neurons were compared to rank order of E max values for cyclase assays in HEK cells. Comparison revealed a significant reversal in rank order for cyclase E max values and βarr-dependent internalization in neurons, indicating that these responses were ligand-specific. Despite this evidence, and because kinases involved in internalization were not the same across cellular backgrounds, it is not possible to assert if the magnitude and nature of bias revealed by rank orders of maximal responses is the same as the one measured in HEK cells.
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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.