ArticleMolecular pharmacology2012
Endomorphin-2: a biased agonist at the μ-opioid receptor.
Article in Molecular pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
62 citing papers in PubMed, 99 citations in OpenAlex.
- Discovery of putative G-protein-biased µ-opioid agonists via hierarchical virtual screening of ultra-large chemical space.Molecular diversity · 2026Article
- Narrative review of the scientific and methodological explanations for 101 mechanisms of opioid tolerance.Pain reports · 2025Article
- Effects of two structurally diverse positive allosteric modulators on signaling bias at the μ-opioid receptor.Molecular pharmacology · 2025Article
- Rational Design Biased Compounds against μ‑Opioid Receptor.ACS pharmacology & translational science · 2025Article
- Opioid Analgesics: Rise and Fall of Ligand Biased Signaling and Future Perspectives in the Quest for the Holy Grail.CNS drugs · 2025Review
- Slow dissociation kinetics of fentanyls and nitazenes correlates with reduced sensitivity to naloxone reversal at the μ-opioid receptor.British journal of pharmacology · 2025Article
- Comparison of the reinforcing, antinociceptive, and respiratory depressant effects of prototypical and G-protein biased mu-opioid receptor agonists in male and female Sprague-Dawley rats.Psychopharmacology · 2024Article
- Effect of antipsychotic drugs on group II metabotropic glutamate receptor expression and epigenetic control in postmortem brains of schizophrenia subjects.Translational psychiatry · 2024Article
- Disinhibition does not play a role in endomorphin-2-induced changes in inspiratory motoneuron output produced by in vitro neonatal rat preparations.Respiratory physiology & neurobiology · 2024Article
- IUPHAR themed review: Opioid efficacy, bias, and selectivity.Pharmacological research · 2023Review
- Carfentanil is a β-arrestin-biased agonist at the μ opioid receptor.British journal of pharmacology · 2023Article
- Arbiters of endogenous opioid analgesia: role of CNS estrogenic and glutamatergic systems.Translational research : the journal of laboratory and clinical medicine · 2021Review
- Comprehensive overview of biased pharmacology at the opioid receptors: biased ligands and bias factors.RSC medicinal chemistry · 2021Review
- Positive allosteric modulation of the mu-opioid receptor produces analgesia with reduced side effects.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Quantifying the Kinetics of Signaling and Arrestin Recruitment by Nervous System G-Protein Coupled Receptors.Frontiers in cellular neuroscience · 2021Article
- Recent Progress in Opioid Research from an Electrophysiological Perspective.Molecular pharmacology · 2020Review
- Morphine-induced respiratory depression is independent of β-arrestin2 signalling.British journal of pharmacology · 2020Article
- Commentary on "Morphine-induced respiratory depression is independent of β-arrestin2 signalling".British journal of pharmacology · 2020Article
- β-Arrestin 2 and ERK1/2 Are Important Mediators Engaged in Close Cooperation between TRPV1 and µ-Opioid Receptors in the Plasma Membrane.International journal of molecular sciences · 2020Article
- In Vitro Effects of Ligand Bias on Primate Mu Opioid Receptor Downstream Signaling.International journal of molecular sciences · 2020Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Previously we correlated the efficacy for G protein activation with that for arrestin recruitment for a number of agonists at the μ-opioid receptor (MOPr) stably expressed in HEK293 cells. We suggested that the endomorphins (endomorphin-1 and -2) might be biased toward arrestin recruitment. In the present study, we investigated this phenomenon in more detail for endomorphin-2, using endogenous MOPr in rat brain as well as MOPr stably expressed in HEK293 cells. For MOPr in neurons in brainstem locus ceruleus slices, the peptide agonists [d-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO) and endomorphin-2 activated inwardly rectifying K(+) current in a concentration-dependent manner. Analysis of these responses with the operational model of pharmacological agonism confirmed that endomorphin-2 had a much lower operational efficacy for G protein-mediated responses than did DAMGO at native MOPr in mature neurons. However, endomorphin-2 induced faster desensitization of the K(+) current than did DAMGO. In addition, in HEK293 cells stably expressing MOPr, the ability of endomorphin-2 to induce phosphorylation of Ser375 in the COOH terminus of the receptor, to induce association of arrestin with the receptor, and to induce cell surface loss of receptors was much more efficient than would be predicted from its efficacy for G protein-mediated signaling. Together, these results indicate that endomorphin-2 is an arrestin-biased agonist at MOPr and the reason for this is likely to be the ability of endomorphin-2 to induce greater phosphorylation of MOPr than would be expected from its ability to activate MOPr and to induce activation of G proteins.
Indexed as
Identifiers
What OpenQuestion holds
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.