ArticleThe Journal of biological chemistry2013
Ligands raise the constraint that limits constitutive activation in G protein-coupled opioid receptors.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Opportunities and Challenges for In Silico Drug Discovery at Delta Opioid Receptors.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Pharmacology of Kappa Opioid Receptors: Novel Assays and Ligands.Frontiers in pharmacology · 2022Article
- Biased Opioid Ligands.Molecules (Basel, Switzerland) · 2020Review
- Vasopressin receptor 2 mutations in the nephrogenic syndrome of inappropriate antidiuresis show different mechanisms of constitutive activation for G protein coupled receptors.Scientific reports · 2020Article
- The Meta-Position of PheMolecules (Basel, Switzerland) · 2019Article
- Therapeutic Potential of Targeting ß-Arrestin.Frontiers in pharmacology · 2019Review
- A Receptor Model With Binding Affinity, Activation Efficacy, and Signal Amplification Parameters for Complex Fractional Response Versus Occupancy Data.Frontiers in pharmacology · 2019Article
- Allosteric nanobodies reveal the dynamic range and diverse mechanisms of G-protein-coupled receptor activation.Nature · 2016Article
- In Vitro Effects of the Endocrine Disruptor p,p'-DDT on Human Follitropin Receptor.Environmental health perspectives · 2016Article
- Molecular Pharmacology of δ-Opioid Receptors.Pharmacological reviews · 2016Review
- Nociceptin/Orphanin FQ Receptor Structure, Signaling, Ligands, Functions, and Interactions with Opioid Systems.Pharmacological reviews · 2016Review
- Sustained Suppression of Hyperalgesia during Latent Sensitization by μ-, δ-, and κ-opioid receptors and α2A Adrenergic Receptors: Role of Constitutive Activity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Latent sensitization: a model for stress-sensitive chronic pain.Current protocols in neuroscience · 2015Article
- Pharmacological Profile of Nociceptin/Orphanin FQ Receptors Interacting with G-Proteins and β-Arrestins 2.PloS one · 2015Article
- The atypical antidepressant and neurorestorative agent tianeptine is a μ-opioid receptor agonist.Translational psychiatry · 2014Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Using a cell-free bioluminescence resonance energy transfer strategy we compared the levels of spontaneous and ligand-induced receptor-G protein coupling in δ (DOP) and μ (MOP) opioid receptors. In this assay GDP can suppress spontaneous coupling, thus allowing its quantification. The level of constitutive activity was 4-5 times greater at the DOP than at the MOP receptor. A series of opioid analogues with a common peptidomimetic scaffold displayed remarkable inversions of efficacy in the two receptors. Agonists that enhanced coupling above the low intrinsic level of the MOP receptor were inverse agonists in reducing the greater level of constitutive coupling of the DOP receptor. Yet the intrinsic activities of such ligands are identical when scaled over the GDP base line of both receptors. This pattern is in conflict with the predictions of the ternary complex model and the "two state" extensions. According to this theory, the order of spontaneous and ligand-induced coupling cannot be reversed if a shift of the equilibrium between active and inactive forms raises constitutive activation in one receptor type. We propose that constitutive activation results from a lessened intrinsic barrier that restrains spontaneous coupling. Any ligand, regardless of its efficacy, must enhance this constraint to stabilize the ligand-bound complexed form.
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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.