ArticleMolecular pharmacology2012
Allosteric interactions between δ and κ opioid receptors in peripheral sensory neurons.
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 39 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
39 citing papers in PubMed, 60 citations in OpenAlex.
- Kappa opioid receptor antagonism in neuropsychiatry: from molecular mechanisms to clinical prospects.European archives of psychiatry and clinical neuroscience · 2026Review
- Single-molecule characterization of opioid receptor heterodimers reveals soluble µ-δ dimer blocker peptide alleviates morphine tolerance.Nature communications · 2025Article
- Activation of G protein gated inwardly rectifying potassium (GIRK) channels in keratinocytes mediates peripheral kappa opioid receptor-mediated antinociception.Neuropharmacology · 2025Article
- IUPHAR themed review: Opioid efficacy, bias, and selectivity.Pharmacological research · 2023Review
- 14-3-3γ mediates the long-term inhibition of peripheral kappa opioid receptor antinociceptive signaling by norbinaltorphimine.Neuropharmacology · 2022Article
- Age-related changes in peripheral nociceptor function.Neuropharmacology · 2022Article
- Exploiting Injury-Induced Peripheral Opioid Receptor Changes in Novel Analgesic Development for Chronic Pain.Frontiers in pain research (Lausanne, Switzerland) · 2022Article
- Long-term antagonism and allosteric regulation of mu opioid receptors by the novel ligand, methocinnamox.Pharmacology research & perspectives · 2021Article
- Dual-Acting Peripherally Restricted Delta/Kappa Opioid (CAV1001) Produces Antinociception in Animal Models of Sub-Acute and Chronic Pain.Journal of pain research · 2020Article
- Signaling characteristics and functional regulation of delta opioid-kappa opioid receptor (DOP-KOP) heteromers in peripheral sensory neurons.Neuropharmacology · 2019Article
- Making Sense of Pharmacology: Inverse Agonism and Functional Selectivity.The international journal of neuropsychopharmacology · 2018Review
- Targeting opioid receptor signaling in depression: do we need selective κ opioid receptor antagonists?Neuronal signaling · 2018Review
- Allosterism withinMolecular pharmacology · 2018Article
- Heteromers of μ opioid and dopamine DBritish journal of pharmacology · 2017Article
- Regulation of δ Opioid Receptor-Mediated Signaling and Antinociception in Peripheral Sensory Neurons by Arachidonic Acid-Dependent 12/15-Lipoxygenase Metabolites.The Journal of pharmacology and experimental therapeutics · 2017Article
- Recent Advances in the Realm of Allosteric Modulators for Opioid Receptors for Future Therapeutics.ACS chemical neuroscience · 2017Review
- Identification of a signaling cascade that maintains constitutive δ-opioid receptor incompetence in peripheral sensory neurons.The Journal of biological chemistry · 2017Article
- Detection of Receptor Heteromerization Using In Situ Proximity Ligation Assay.Current protocols in pharmacology · 2016Article
- Constitutive Desensitization of Opioid Receptors in Peripheral Sensory Neurons.The Journal of pharmacology and experimental therapeutics · 2016Article
- Molecular signatures of mu opioid receptor and somatostatin receptor 2 in pancreatic cancer.Molecular biology of the cell · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
The peripheral δ opioid receptor (DOR) is an attractive target for analgesic drug development. There is evidence that DOR can form heteromers with the κ-opioid receptor (KOR). As drug targets, heteromeric receptors offer an additional level of selectivity and, because of allosteric interactions between protomers, functionality. Here we report that selective KOR antagonists differentially altered the potency and/or efficacy of DOR agonists in primary cultures of adult rat peripheral sensory neurons and in a rat behavioral model of thermal allodynia. In vitro, the KOR antagonist nor-binaltorphimine (nor-BNI) enhanced the potency of [D-Pen(2,5)]-enkephalin (DPDPE), decreased the potency of [D-Ala(2),D-Leu(5)]-enkephalin (DADLE), and decreased the potency and efficacy of 4-[(R)-[(2S,5R)-4-allyl-2,5-dimethylpiperazin-1-yl](3-methoxyphenyl)methyl]-N,N-diethylbenzamide (SNC80) to inhibit prostaglandin E(2) (PGE(2))-stimulated adenylyl cyclase activity. In vivo, nor-BNI enhanced the effect of DPDPE and decreased the effect of SNC80 to inhibit PGE(2)-stimulated thermal allodynia. In contrast to nor-BNI, the KOR antagonist 5'-guanidinonaltrindole (5'-GNTI) reduced the response of DPDPE both in cultured neurons and in vivo. Evidence for DOR-KOR heteromers in peripheral sensory neurons included coimmunoprecipitation of DOR with KOR, a DOR-KOR heteromer selective antibody augmented the antinociceptive effect of DPDPE in vivo, and the DOR-KOR heteromer agonist 6'-GNTI inhibited adenylyl cyclase activity in vitro as well as PGE(2)-stimulated thermal allodynia in vivo. Taken together, these data suggest that DOR-KOR heteromers exist in rat primary sensory neurons and that KOR antagonists can act as modulators of DOR agonist responses most likely through allosteric interactions between the protomers of the DOR-KOR heteromer.
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.