Affinage

OPRK1

Kappa-type opioid receptor · UniProt P41145

Length
380 aa
Mass
42.6 kDa
Annotated
2026-04-29
100 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

OPRK1 encodes the kappa opioid receptor (KOR), a Gαi/o-coupled GPCR activated by dynorphin peptides and selective synthetic agonists such as U50,488H that functions as a central modulator of nociception, aversion, reward, and affective behavior. KOR activation inhibits cAMP production — requiring adenylyl cyclase 3 in peripheral sensory neurons — and engages downstream ERK1/2, p38 MAPK, mTOR, and STAT3 signaling pathways; agonist-stimulated GRK phosphorylation at C-terminal residues (including Ser369) initiates β-arrestin-dependent desensitization, with phosphorylation-site mutations revealing sex-dependent roles in tolerance and conditioned place aversion (PMID:34736959, PMID:21370032, PMID:34914639, PMID:22424981). Within the mesolimbic dopamine system, VTA KOR activation suppresses striatal dopamine release to drive aversive learning and avoidance behavior, and cell-type-specific KOR overexpression in VTA dopaminergic neurons is sufficient to escalate alcohol self-administration and produce depressive-like phenotypes (PMID:32057802, PMID:36764577). OPRK1 transcription is repressed by a functional promoter insertion/deletion variant and by CpG methylation, and post-transcriptionally suppressed by miR-144-3p targeting the 3′UTR (PMID:18319328, PMID:26300544, PMID:37455648).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1999 Medium

    Antisense exon mapping revealed that endogenous dynorphin peptides and synthetic KOR agonists engage distinct receptor mechanisms despite shared antagonist sensitivity, establishing that OPRK1 gene products can mediate pharmacologically distinguishable kappa opioid activities.

    Evidence Antisense oligodeoxynucleotide targeting of KOR-1 exons in mouse analgesia models with multiple ligands

    PMID:10224306

    Open questions at the time
    • Molecular identity of the kappa1b site was not resolved
    • No receptor mutagenesis or binding data to confirm distinct receptor configurations
  2. 2006 Medium

    Identification of KOR expression predominantly on GABAergic OFF and NEUTRAL cells in the rostral ventromedial medulla established a circuit-level mechanism for KOR modulation of descending pain control.

    Evidence Juxtacellular labeling with immunofluorescence for KOR and GAD67 in functionally classified RVM neurons in vivo

    PMID:17005613

    Open questions at the time
    • Functional consequence of KOR activation on these specific cell types was not directly tested electrophysiologically
    • Whether RVM KOR modulates affective versus sensory pain dimensions was not addressed
  3. 2008 High

    A functional insertion/deletion variant upstream of the OPRK1 coding region was shown to halve transcriptional activity, providing the first direct evidence that cis-regulatory variation modulates KOR expression levels.

    Evidence Luciferase reporter promoter assays with allele-specific constructs

    PMID:18319328

    Open questions at the time
    • Effect on endogenous KOR protein levels in human tissue not demonstrated
    • Association with addiction phenotypes was suggestive but not definitive
  4. 2011 Medium

    Development and validation of phospho-Ser369-specific antibodies confirmed that GRK-mediated phosphorylation of KOR's C-terminal tail is an in vivo marker of receptor activation, linking agonist exposure and stress to a defined post-translational modification.

    Evidence Phospho-selective antibody immunohistochemistry following behavioral and pharmacological manipulation in rodents

    PMID:21370032

    Open questions at the time
    • Contribution of specific GRK isoforms was not determined
    • Downstream consequences of Ser369 phosphorylation beyond β-arrestin recruitment were not dissected
  5. 2012 Medium

    Demonstration that KOR on macrophages signals through ERK1/2 upon dynorphin-A stimulation, with IFN-γ upregulating KOR expression, extended KOR function beyond neurons to immune cells.

    Evidence Western blot for phospho-ERK1/2 in J774 macrophages stimulated with Dynorphin-A(1-17) vs. truncated control

    PMID:22424981

    Open questions at the time
    • Physiological relevance of macrophage KOR signaling in vivo not established
    • Whether ERK activation leads to cytokine modulation was not tested
  6. 2015 High

    Three advances refined KOR biology: crystal structures of inactive (JDTic-bound) KOR revealed subtype selectivity determinants; CpG methylation of the OPRK1 promoter was shown to suppress transcription; and KOR-Cre knockin mice mapped KOR expression across brain regions and peripheral tissues from embryonic day 14.5.

    Evidence X-ray crystallography; luciferase reporter assay with bisulphite pyrosequencing; Cre-reporter recombination mapping in knockin mice

    PMID:26160155 PMID:26300544 PMID:26575788 PMID:33945028

    Open questions at the time
    • Active-state KOR structure dynamics and G protein coupling interface not fully resolved at this time
    • Functional consequences of KOR expression in non-neuronal tissues remain largely unexplored
  7. 2020 High

    Intra-VTA KOR blockade attenuated real-time dopamine decreases and avoidance behavior, placing VTA KOR upstream of striatal dopamine signaling in aversion-driven learned avoidance and defining a circuit mechanism for KOR-mediated dysphoria.

    Evidence Site-specific norBNI infusion with fast-scan cyclic voltammetry for dopamine and behavioral avoidance assay in rats

    PMID:32057802

    Open questions at the time
    • Cell-type specificity of VTA KOR (dopaminergic vs. GABAergic neurons) was not resolved
    • Whether this circuit mediates stress-induced relapse to drug seeking was not directly tested
  8. 2021 High

    Knockin mice lacking four C-terminal KOR phosphorylation sites revealed that receptor phosphorylation mediates tolerance and conditioned place aversion in a sex-dependent manner, dissociating phosphorylation-dependent from phosphorylation-independent behavioral outputs.

    Evidence K4A knockin mice with behavioral pharmacology (anti-scratch tolerance, conditioned place aversion, locomotion)

    PMID:34736959

    Open questions at the time
    • Molecular basis for the sex difference (hormonal vs. circuit) was not identified
    • Which of the four residues is most critical was not resolved
  9. 2022 High

    Multiple studies in 2022 expanded the KOR signaling repertoire: AC3 was identified as essential for peripheral KOR/Gαi-o coupling to Kv channels and analgesia; dynorphin/KOR was shown to inhibit autophagy via mTOR; KOR overexpression in VTA DA neurons recapitulated alcohol dependence phenotypes; and central vs. peripheral KOR pathways were pharmacologically dissected for diuresis vs. electrolyte handling.

    Evidence AC3 conditional KO with electrophysiology; prodynorphin overexpression with rapamycin rescue in epilepsy models; Cre-Lox Oprk1 overexpression in TH::Cre rats; ICV vs. IV norBNI with renal function readouts

    PMID:34914639 PMID:35989483 PMID:36202183 PMID:36764577

    Open questions at the time
    • Whether AC3-KOR interaction is direct or scaffolded remains unclear
    • mTOR pathway activation by KOR needs confirmation beyond epilepsy context
    • How VTA KOR overexpression interacts with endogenous dynorphin tone is unknown
  10. 2023 Medium

    Post-transcriptional regulation of OPRK1 by miR-144-3p was validated, and KOR's circuit-level role in pain-aversive memory was placed upstream of insular cortex GABAergic neurons, while KOR/STAT3 signaling was linked to oligodendrocyte precursor cell maturation and remyelination.

    Evidence Luciferase 3′UTR reporter assay for miR-144-3p; DREADD chemogenetics with intra-insular KOR pharmacology; virtual screening with in vitro OPC differentiation and in vivo demyelination models

    PMID:37455648 PMID:37679857 PMID:38692525

    Open questions at the time
    • miR-144-3p regulation of OPRK1 not confirmed in human tissue
    • KOR/STAT3 pathway in remyelination demonstrated with repurposed drug (famotidine) whose selectivity for KOR over H2R in vivo needs clarification
    • Insular cortex findings are from a single pain model

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of biased agonism at KOR (G protein vs. β-arrestin pathways), the molecular determinants of sex-dependent KOR phosphorylation effects, the physiological roles of KOR in non-neuronal tissues identified by expression mapping, and whether KOR-targeted therapies can achieve pathway-selective efficacy in humans.
  • No human clinical validation of biased KOR agonism for dissociating therapeutic from adverse effects
  • Structural basis for agonist-induced conformational bias at KOR not resolved at atomic level
  • KOR function in peripheral immune and epithelial cells remains largely unexplored mechanistically

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-112316 Neuronal System 4 R-HSA-9612973 Autophagy 1
Partners
ADCY3ARRB2GRK3MTORPDYNSTAT3

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 An insertion/deletion variant located ~1986 bp upstream of the OPRK1 translation start site functions as a regulatory element; the longer allele (with the indel) reduced OPRK1 transcriptional activity by approximately half in transient transfection promoter assays, establishing this as a functional regulatory variation affecting KOR expression levels. Transient transfection promoter assay (luciferase reporter), PCR genotyping, family-based association analysis Human molecular genetics High 18319328
2015 OPRK1 promoter hypermethylation reduces OPRK1 gene expression; luciferase reporter assay demonstrated that a CpG-containing fragment of the OPRK1 promoter significantly increased reporter gene expression (~2.25-fold), indicating that methylation of this region suppresses KOR expression. Bisulphite pyrosequencing for methylation quantification; luciferase reporter gene assay Neuroscience letters Medium 26300544
2011 KOR (encoded by OPRK1) is phosphorylated at Ser369 in its C-terminal tail by G protein receptor kinase (GRK) upon agonist activation, initiating the β-arrestin-dependent desensitization cascade; phospho-selective antibodies against this site were developed and validated to track KOR activation in vivo following stress or behavioral stimuli. Phospho-selective antibody development and immunohistochemical validation; behavioral and pharmacological manipulation in rodents Methods in molecular biology Medium 21370032
2021 Agonist-promoted phosphorylation of mouse KOR at four C-terminal residues (mutated to Ala in K4A mice) plays sex-dependent roles in tolerance and conditioned place aversion (CPA): male K4A mice showed attenuated tolerance to anti-scratch effects and retained CPA to U50,488H, while female K4A mice showed no CPA, revealing that KOR phosphorylation mediates behavioral endpoints in a sex-specific manner without affecting acute anti-pruritic or hypo-locomotor effects. Knockin mouse (K4A mutant), autoradiography ([3H]U69,593 binding), behavioral assays (scratch, locomotion, conditioned place aversion, tolerance), in vivo pharmacology Neuropharmacology High 34736959
2022 Peripheral conditional knockout of adenylyl cyclase 3 (AC3) in DRGs eliminated the analgesic effect of a KOR agonist and blocked KOR-mediated inhibition of voltage-gated potassium (Kv) channels, demonstrating that AC3 is required for KOR/Gαi-o signaling and possibly via direct KOR-AC3 protein interaction in peripheral sensory neurons. Conditional KO (AC3 CKO in L3/L4 DRGs), Kv channel current recordings, cAMP measurements, behavioral nociception assays, Western blot, pharmacological rescue JCI insight High 34914639
2012 KOR expressed on murine macrophage J774 cells is functionally active: ligation with Dynorphin-A(1-17) (but not truncated Dynorphin-A(2-17) which lacks KOR binding) triggers ERK1/2 phosphorylation, and IFN-γ upregulates KOR expression at both transcriptional and protein levels. FACS, immunocytochemistry, Western blot (ERK1/2 phosphorylation), RT-PCR, IFN-γ stimulation Journal of neuroimmunology Medium 22424981
2015 KOR-Cre knockin mice, in which Cre replaces the initial OPRK1 coding sequence, revealed that KOR is expressed in cerebral cortex, nucleus accumbens, striatum, as well as non-neuronal tissues including epithelium, heart, lung, liver, and retinal bipolar/amacrine cells, with recombination detectable by embryonic day 14.5. Knockin mouse (Cre recombinase replacing Oprk1 coding sequence), reporter recombination assay, immunohistochemistry, live imaging Genesis Medium 26575788
2015 Dynorphin peptides promiscuously stimulate G protein signaling (measured by [35S]GTPγS binding) at multiple receptors in striatal membranes and are not selective for KOR; by contrast, the small-molecule agonist U69,593 is highly selective for KOR in this endogenous system. norBNI and 5'GNTI maintain full potency and efficacy against dynorphin-stimulated signaling even in KOR knockout striatum, demonstrating their non-selectivity for KOR in this context. [35S]GTPγS binding assay in striatal membrane preparations from WT, KOR-KO, and MOR-KO mice; pharmacological characterization of agonists and antagonists Neuropharmacology High 26160155
2020 VTA KOR activation mediates aversion-induced reductions in striatal dopamine required for learned avoidance: intra-VTA KOR blockade attenuated real-time aversion-induced dopamine decreases and prevented avoidance behavior; intra-nucleus accumbens D2 receptor agonism (mimicking reduced dopamine tone) also prevented avoidance, placing VTA KOR upstream of dopamine-dependent striatal aversion circuitry. Site-specific pharmacology (intra-VTA norBNI), real-time dopamine voltammetry, intra-NAc D2 agonism, behavioral avoidance assay in rats Neuropharmacology High 32057802
2022 The KOR structure in complex with the antagonist JDTic (crystal structure solved in 2012) and a more recent active-state KOR structure together reveal atomic details of the ligand binding pocket, subtype selectivity determinants, and receptor activation mechanisms including distinct contacts for agonists versus antagonists. X-ray crystallography (inactive state with JDTic); structural determination of active state KOR Handbook of experimental pharmacology High 33945028
2023 Activation of KOR by famotidine (identified via structure-based virtual screening) promotes oligodendrocyte precursor cell (OPC) maturation and CNS remyelination through the KOR/STAT3 signaling pathway, as demonstrated in vitro and in vivo demyelinating disease models. Structure-based virtual screening, in vitro OPC differentiation assays, in vivo remyelination model, Western blot (STAT3 pathway), pharmacological validation International journal of biological macromolecules Medium 38692525
2022 Overexpression of Oprk1 in VTA dopaminergic neurons (using TH::Cre rats with conditional inducible Cre-Lox system) recapitulated phenotypes of alcohol dependence, including escalated alcohol self-administration and depressive-like behavior, demonstrating that KOR signaling specifically within VTA DA neurons is sufficient to drive maladaptive behavioral regulation associated with alcohol dependence. Conditional Oprk1 overexpression (Cre-Lox in TH::Cre rats), operant alcohol self-administration, affective behavior assays, RT-PCR and functional KOR assays in VTA Neuropharmacology Medium 36764577
2022 Activation of KOR inhibits estrogen receptor (ER)-positive breast cancer cell proliferation and promotes apoptosis; gene ontology and PPI network analysis followed by XBP1 silencing experiments identified KOR-ER-XBP1 as the downstream signaling pathway mediating the anti-tumor effects of KOR agonists in MCF-7 and T47D cells. Cell viability and apoptosis assays in ER+ breast cancer cell lines, siRNA knockdown of XBP1, GO/KEGG pathway analysis, PPI network analysis Biomedicine & pharmacotherapy Medium 37708692
2016 KOR knockout (KOR-KO) mice showed significantly increased mechanical allodynia after intra-articular MIA injection compared to WT mice, and demonstrated increased microglial activation in the lumbar spinal cord, alterations in CRF in the amygdala and hippocampus, and down-regulation of histone 3 acetylation in the amygdala, establishing the dynorphin/KOR system's role in modulating nociceptive, emotional, and cognitive dimensions of joint pain. KOR-KO and PDYN-KO mice, MIA joint pain model, behavioral tests (elevated plus maze, object recognition, anhedonia), immunohistochemistry, Western blot Neuropharmacology Medium 27567942
1999 Antisense oligodeoxynucleotide mapping of the three exons of KOR-1 revealed that analgesia produced by dynorphin B and alpha-neoendorphin differs mechanistically from U50,488H analgesia: probes targeting all three exons blocked U50,488H analgesia, while dynorphin B and alpha-neoendorphin showed distinct antisense probe selectivity profiles, indicating they act via different receptor mechanisms (kappa1b site) despite sharing sensitivity to norBNI. Antisense oligodeoxynucleotide exon mapping in vivo (mouse analgesia), kappa1-selective antagonist (norBNI) challenge Brain research Medium 10224306
2023 miR-144-3p directly suppresses Oprk1/KOR expression: luciferase assay confirmed that miR-144-3p exerts an inhibitory effect on Oprk1 expression in PC12 cells; nicotine dependence and withdrawal decreased miR-144-3p and increased Oprk1/KOR in prefrontal cortex, nucleus accumbens, and hippocampus. miRNA sequencing, qRT-PCR, Western blot, luciferase reporter assay for miR-144-3p/Oprk1 interaction Nicotine & tobacco research Medium 37455648
2023 Activation of KOR in the insular cortex blocked pain-related aversive memory behaviors, and subsequent experiments showed that activation of GABAergic neurons in the insular cortex reversed the effect of KOR activation, placing KOR upstream of GABAergic neuron activity in this circuit; electroacupuncture-mediated block of pain aversive memory was reversed by either GABAergic neuron activation or KOR inhibition in the insular cortex. Chemogenetics (DREADD), pharmacology (KOR agonist/antagonist injection into insular cortex), behavioral assays (carrageenan pain-aversive memory model) in mice Cerebral cortex Medium 37679857
2022 Difelikefalin (peripherally restricted KOR agonist) produces diuresis predominantly through central KOR pathways: ICV norBNI (central KOR blockade) markedly attenuated difelikefalin-induced urine output, while peripheral norBNI prevented all responses; electrolyte reabsorption effects were mediated through peripheral KOR pathways, demonstrating distinct central vs. peripheral KOR pathway functions for diuresis and electrolyte handling. ICV vs. IV norBNI pretreatment in conscious catheterized rats, urine output and electrolyte measurements, cardiovascular monitoring Pharmacological research Medium 36202183
2006 KOR immunoreactivity was found predominantly in OFF (86%) and NEUTRAL (80%) cells but rarely in ON (13%) cells in the rostral ventromedial medulla (RVM); most KOR-immunoreactive cells (16 of 17) also contained GAD67, identifying KOR-expressing neurons in the RVM as predominantly GABAergic, consistent with KOR agonists directly inhibiting off and neutral cell activity. Extracellular recording of RVM neurons in vivo, juxtacellular biotinamide labeling, immunofluorescence for KOR and GAD67 Journal of neurophysiology Medium 17005613
2022 Dynorphin/KOR system inhibits neuronal autophagy by activating the mTOR signaling pathway: overexpression of prodynorphin in epileptic rats activated mTOR, inhibited autophagy markers (LC3, GFP-LC3 puncta), and reduced neuronal apoptosis; rapamycin (mTOR inhibitor) reversed the dynorphin/KOR-mediated anti-autophagy and anti-apoptotic effects in Mg2+-free-induced seizure-like neurons. Prodynorphin overexpression in vivo (pilocarpine epilepsy model), Mg2+-free in vitro seizure model, Western blot (mTOR pathway), TUNEL/flow cytometry apoptosis, GFP-LC3 autophagy assay, pharmacological rescue with rapamycin Cell biology international Medium 35989483
2025 Triazole 187, a G protein signaling-biased KOR agonist, suppresses itch without sedation (no reduction in spontaneous locomotion) and produces anxiolytic-like behaviors, demonstrating that G protein-biased KOR agonism can dissociate antipruritic effects from sedation; it also produces markedly less diuresis (30% of U50,488H at 188-fold the antipruritic potency dose) compared to unbiased KOR agonists. In vitro G protein/β-arrestin signaling assays, behavioral pharmacology (locomotion, itch, anxiety, diuresis) in mice bioRxivpreprint Medium 40027836

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Opioid receptor gene (OPRM1, OPRK1, and OPRD1) variants and response to naltrexone treatment for alcohol dependence: results from the VA Cooperative Study. Alcoholism, clinical and experimental research 171 17374034
2004 Redefinition of the human kappa opioid receptor gene (OPRK1) structure and association of haplotypes with opiate addiction. Pharmacogenetics 83 15608558
1983 Deletion mapping of kil and kor functions in the trfA and trfB regions of broad host range plasmid RK2. Molecular & general genetics : MGG 75 6308390
1985 Replication control in promiscuous plasmid RK2: kil and kor functions affect expression of the essential replication gene trfA. Journal of bacteriology 69 3891728
1995 The outer membrane protein OprM of Pseudomonas aeruginosa is encoded by oprK of the mexA-mexB-oprK multidrug resistance operon. Antimicrobial agents and chemotherapy 67 8585747
1987 Plasmid transfer in Streptomyces lividans: identification of a kil-kor system associated with the transfer region of pIJ101. Journal of bacteriology 67 3040681
2006 Kappa opioid receptor (KOR) and GAD67 immunoreactivity are found in OFF and NEUTRAL cells in the rostral ventromedial medulla. Journal of neurophysiology 63 17005613
2007 Human kappa opioid receptor gene (OPRK1) polymorphism is associated with opiate addiction. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 60 17373729
1989 Identification and analysis of transcriptional regulatory signals for the kil and kor loci of Streptomyces plasmid pIJ101. Journal of bacteriology 60 2681140
1993 Transfer functions of the conjugative integrating element pSAM2 from Streptomyces ambofaciens: characterization of a kil-kor system associated with transfer. Journal of bacteriology 52 8366038
2008 A regulatory variation in OPRK1, the gene encoding the kappa-opioid receptor, is associated with alcohol dependence. Human molecular genetics 51 18319328
2022 Major Bloodstream Infection-Causing Bacterial Pathogens and Their Antimicrobial Resistance in South Korea, 2017-2019: Phase I Report From Kor-GLASS. Frontiers in microbiology 50 35069503
1995 OprK and OprM define two genetically distinct multidrug efflux systems in Pseudomonas aeruginosa. Antimicrobial agents and chemotherapy 48 8585714
2013 A variant on the kappa opioid receptor gene (OPRK1) is associated with stress response and related drug craving, limbic brain activation and cocaine relapse risk. Translational psychiatry 45 23962922
2004 Recombinant expression and enzymatic characterization of PttCel9A, a KOR homologue from Populus tremula x tremuloides. Biochemistry 45 15287736
2019 Design and Synthesis of a Novel and Selective Kappa Opioid Receptor (KOR) Antagonist (BTRX-335140). Journal of medicinal chemistry 42 30707578
1998 Identification and differential regional expression of KOR-3/ORL-1 gene splice variants in mouse brain. FEBS letters 40 9755860
2016 Involvement of the dynorphin/KOR system on the nociceptive, emotional and cognitive manifestations of joint pain in mice. Neuropharmacology 34 27567942
2010 Chicken collagen hydrolysate reduces proinflammatory cytokine production in C57BL/6.KOR-ApoEshl mice. Journal of nutritional science and vitaminology 31 20651463
1995 A novel monoclonal antibody, KOR-SA3544 which reacts to Philadelphia chromosome-positive acute lymphoblastic leukemia cells with high sensitivity. Leukemia 31 7543176
1990 The kil-kor regulon of broad-host-range plasmid RK2: nucleotide sequence, polypeptide product, and expression of regulatory gene korC. Journal of bacteriology 29 2160936
2015 OPRK1 promoter hypermethylation increases the risk of Alzheimer's disease. Neuroscience letters 27 26300544
2015 Synthesis of mixed MOR/KOR efficacy cyclic opioid peptide analogs with antinociceptive activity after systemic administration. European journal of medicinal chemistry 27 26785295
2011 Oral infection with Porphyromonas gingivalis and systemic cytokine profile in C57BL/6.KOR-ApoE shl mice. Journal of periodontal research 27 22097957
2022 Preclinical Studies on Nalfurafine (TRK-820), a Clinically Used KOR Agonist. Handbook of experimental pharmacology 26 33834276
2015 Characterization of kappa opioid receptor mediated, dynorphin-stimulated [35S]GTPγS binding in mouse striatum for the evaluation of selective KOR ligands in an endogenous setting. Neuropharmacology 26 26160155
1998 Aberrant expression of KOR-SA3544 antigen in childhood acute lymphoblastic leukemia predicts TEL-AML1 negativity. The Pediatric Hematology Working Group in the Czech Republic. Leukemia 26 9665191
1993 kil-kor regulon of promiscuous plasmid RK2: structure, products, and regulation of two operons that constitute the kilE locus. Journal of bacteriology 26 8349548
2015 Parallel Synthesis of Hexahydrodiimidazodiazepines Heterocyclic Peptidomimetics and Their in Vitro and in Vivo Activities at μ (MOR), δ (DOR), and κ (KOR) Opioid Receptors. Journal of medicinal chemistry 24 25996309
1984 Involvement of kil and kor genes in the phenotype of a host-range mutant of RP4. Molecular & general genetics : MGG 24 6097793
2015 Generation of a KOR-Cre knockin mouse strain to study cells involved in kappa opioid signaling. Genesis (New York, N.Y. : 2000) 23 26575788
2022 KOR Control over Addiction Processing: An Exploration of the Mesolimbic Dopamine Pathway. Handbook of experimental pharmacology 21 33301050
1999 The KOR-SA3544 antigen predominantly expressed on the surface of Philadelphia chromosome-positive acute lymphoblastic leukemia cells is nonspecific cross-reacting antigen-50/90 (CD66c) and invariably expressed in cytoplasm of human leukemia cells. Leukemia 20 10374883
2012 IFN-γ up-regulates κ opioid receptors (KOR) on murine macrophage cell line J774. Journal of neuroimmunology 19 22424981
2008 Hypolipidemic effect of young persimmon fruit in C57BL/6.KOR-ApoEshl mice. Bioscience, biotechnology, and biochemistry 19 18838807
2017 Association of OPRK1 gene polymorphisms with opioid dependence in addicted men undergoing methadone treatment in an Iranian population. Journal of addictive diseases 18 28786760
2022 SLL-627 Is a Highly Selective and Potent κ Opioid Receptor (KOR) Agonist with an Unexpected Nonreduction in Locomotor Activity. Journal of medicinal chemistry 17 35900351
2020 Modulation of cocaine-related behaviors by low doses of the potent KOR agonist nalfurafine in male C57BL6 mice. Psychopharmacology 17 32435819
2016 Highly selective non-opioid kappa opioid receptor (KOR) agonist salvinorin A protects against forebrain ischemia-induced brain injury in rats. Brain research 17 26907190
2004 Effect of n-3 fatty acids on serum lipid levels and hepatic fatty acid metabolism in BALB/c.KOR-Apoeshl mice deficient in apolipoprotein E expression. The Journal of nutritional biochemistry 17 15023399
2022 Nationwide Surveillance of Antifungal Resistance of Candida Bloodstream Isolates in South Korean Hospitals: Two Year Report from Kor-GLASS. Journal of fungi (Basel, Switzerland) 16 36294562
2016 CB1 receptor antagonism prevents long-term hyperexcitability after head injury by regulation of dynorphin-KOR system and mGluR5 in rat hippocampus. Brain research 16 27262683
2020 Learned avoidance requires VTA KOR-mediated reductions in dopamine. Neuropharmacology 15 32057802
2020 Chemical syntheses of the salvinorin chemotype of KOR agonist. Natural product reports 15 32808003
2021 In Silico Identification of Tripeptides as Lead Compounds for the Design of KOR Ligands. Molecules (Basel, Switzerland) 14 34443366
2018 m-Trifluoromethyl-diphenyl Diselenide Regulates Prefrontal Cortical MOR and KOR Protein Levels and Abolishes the Phenotype Induced by Repeated Forced Swim Stress in Mice. Molecular neurobiology 14 29623611
2023 Machine-learning analysis of opioid use disorder informed by MOR, DOR, KOR, NOR and ZOR-based interactome networks. Computers in biology and medicine 13 36924727
2021 Agonist-promoted kappa opioid receptor (KOR) phosphorylation has behavioral endpoint-dependent and sex-specific effects. Neuropharmacology 13 34736959
2016 Isolation and Characterization of a New Methanobacterium formicicum KOR-1 from an Anaerobic Digester Using Pig Slurry. Asian-Australasian journal of animal sciences 13 26949961
2011 Signaling events initiated by kappa opioid receptor activation: quantification and immunocolocalization using phospho-selective KOR, p38 MAPK, and K(IR) 3.1 antibodies. Methods in molecular biology (Clifton, N.J.) 13 21370032
2001 Expression of a membrane-anchored endo-1,4-beta-glucanase from Brassica napus, orthologous to KOR from Arabidopsis thaliana, is inversely correlated to elongation in light-grown plants. Plant molecular biology 13 11247609
1999 Antisense mapping KOR-1: evidence for multiple kappa analgesic mechanisms. Brain research 13 10224306
1991 Differentiation of lethal and nonlethal, kor-regulated functions in the kilB region of broad host-range plasmid RK2. Plasmid 13 1852017
2022 Peripheral ablation of type III adenylyl cyclase induces hyperalgesia and eliminates KOR-mediated analgesia in mice. JCI insight 12 34914639
2018 O6C-20-nor-salvinorin A is a stable and potent KOR agonist. Bioorganic & medicinal chemistry letters 12 29426768
2017 Stereoselective synthesis of conformationally restricted KOR agonists based on the 2,5-diazabicyclo[2.2.2]octane scaffold. Organic & biomolecular chemistry 12 28745376
2016 6β-N-Heterocyclic Substituted Naltrexamine Derivative BNAP: A Peripherally Selective Mixed MOR/KOR Ligand. ACS chemical neuroscience 12 27269866
2016 Association of OPRK1 and OPRM1 methylation with mild cognitive impairment in Xinjiang Han and Uygur populations. Neuroscience letters 12 27838450
2017 Molecular identification of the Dyn/Kor system and its potential role in the reproductive axis of goldfish. General and comparative endocrinology 11 28242307
2023 Electroacupuncture alleviates the relapse of pain-related aversive memory by activating KOR and inhibiting GABAergic neurons in the insular cortex. Cerebral cortex (New York, N.Y. : 1991) 10 37679857
2023 Activation of kappa opioid receptor (KOR) inhibits estrogen receptor (ER)-positive breast cancer through the KOR-ER-XBP1 pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 9 37708692
2022 Conditional Deletion of KOR (Oprk1) in Kisspeptin Cells Does Not Alter LH Pulses, Puberty, or Fertility in Mice. Endocrinology 9 36260530
2021 Nalfurafine, a G-Protein-Biased KOR (Kappa Opioid Receptor) Agonist, Enhances the Diuretic Response and Limits Electrolyte Losses to Standard-of-Care Diuretics. Hypertension (Dallas, Tex. : 1979) 9 34852633
2020 Synthesis and Pharmacological Evaluation of Fluorinated Quinoxaline-Based κ-Opioid Receptor (KOR) Agonists Designed for PET Studies. ChemMedChem 9 33448685
2014 Synthesis and Pharmacology of a Novel κ Opioid Receptor (KOR) Agonist with a 1,3,5-Trioxazatriquinane Skeleton. ACS medicinal chemistry letters 9 25147605
2022 Dynorphin/KOR inhibits neuronal autophagy by activating mTOR signaling pathway to prevent acute seizure epilepsy. Cell biology international 8 35989483
2022 Discovery of κ Opioid Receptor (KOR)-Selective d-Tetrapeptides with Improved In Vivo Antinociceptive Effect after Peripheral Administration. ACS medicinal chemistry letters 8 36385929
2022 Characterization of a Potential KOR/DOR Dual Agonist with No Apparent Abuse Liability via a Complementary Structure-Activity Relationship Study on Nalfurafine Analogues. ACS chemical neuroscience 8 36449691
2004 Opposite alterations of NPFF1 and NPFF2 neuropeptide FF receptor density in the triple MOR/DOR/KOR-opioid receptor knockout mouse brains. Journal of chemical neuroanatomy 8 15121216
2023 Recapitulating phenotypes of alcohol dependence via overexpression of Oprk1 in the ventral tegmental area of non-dependent TH::Cre rats. Neuropharmacology 7 36764577
2021 Multifunctional Enkephalin Analogs with a New Biological Profile: MOR/DOR Agonism and KOR Antagonism. Biomedicines 7 34072734
2021 Synthesis and pharmacological evaluation of enantiomerically pure endo-configured KOR agonists with 2-azabicyclo[3.2.1]octane scaffold. Organic & biomolecular chemistry 7 34528988
2021 Analyses of polymorphisms of intron 2 of OPRK1 (kappa-opioid receptor gene) in association with opioid and cocaine dependence diagnoses in an African-American population. Neuroscience letters 7 34843875
2017 Isolation and characterization of new Methanosarcina mazei strains KOR-3, -4, -5, and -6 from an anaerobic digester using pig slurry. Asian-Australasian journal of animal sciences 7 28111440
2014 Neurocognitive and neuroinflammatory correlates of PDYN and OPRK1 mRNA expression in the anterior cingulate in postmortem brain of HIV-infected subjects. Journal of neuroinflammation 7 24405578
2018 Isolation and characterization of a new Methanoculleus bourgensis strain KOR-2 from the rumen of Holstein steers. Asian-Australasian journal of animal sciences 6 30056662
2014 A molecular prospective provides new insights into implication of PDYN and OPRK1 genes in alcohol dependence. Computers in biology and medicine 6 25177835
2023 Effect of PDYN and OPRK1 polymorphisms on the risk of alcohol use disorder and the intensity of depressive symptoms. Alcohol and alcoholism (Oxford, Oxfordshire) 5 37177778
2024 Differential methylation of OPRK1 in borderline personality disorder is associated with childhood trauma. Molecular psychiatry 4 38862675
2023 The role of miRNA-144-3p/Oprk1/KOR in nicotine dependence and nicotine withdrawal in male rats. Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco 4 37455648
2022 Difelikefalin, a peripherally restricted KOR (kappa opioid receptor) agonist, produces diuresis through a central KOR pathway. Pharmacological research 4 36202183
2019 Effects of the Alpha-1 Antagonist Prazosin on KOR Agonist-Induced Reinstatement of Alcohol Seeking. The international journal of neuropsychopharmacology 4 31556948
2018 Genetic Variations of OPRM1, OPRK1, and COMT Genes and Their Possible Associations with Oral Pain in a Population from Argentina. Journal of oral & facial pain and headache 4 30365572
2010 Evaluation of the effect of flavangenol on serum lipid peroxide levels and development of atherosclerosis in spontaneously hyperlipidemic B6.KOR-Apoeshl mice. International journal of molecular medicine 4 21069260
2025 KOR agonists for the treatment and/or prevention of opioid use disorder and cocaine use disorder. Pharmacology, biochemistry, and behavior 3 40588011
2024 Targeting of KOR by famotidine promotes OPC maturation differentiation and CNS remyelination via STAT3 signaling pathway. International journal of biological macromolecules 3 38692525
2015 Karyological and molecular analysis of three endemic loaches (Actinopterygii: Cobitoidea) from Kor River basin, Iran. Molecular biology research communications 3 27843991
2025 Structure-activity relationship analysis of meta-substituted N-cyclopropylmethyl-nornepenthones with mixed KOR/MOR activities. European journal of medicinal chemistry 2 40068406
2025 U50 488H KOR agonist reduces cartilage degradation, chondrocyte hypertrophy and bone loss in osteoarthritis. International immunopharmacology 2 40633208
2024 Discovery of N'-benzyl-3-chloro-N-((1S,3R,4R)-3-((dimethylamino)methyl)-4-hydroxy-4-(3-methoxyphenyl)cyclohexyl)benzenesulfonamide as a novel selective KOR ligand. European journal of medicinal chemistry 2 38986343
2023 Clustering of KOR PET images separates people with AUD into distinct responses to naltrexone. Brain imaging and behavior 2 36695971
2023 Association of OPRK1 rs963549 and rs997917 polymorphisms with opioid use disorder and related phenotypes. Pharmacogenomics 2 37166316
2023 Comprehensive behavioral study of C57BL/6.KOR-ApoEshl mice. Translational neuroscience 2 37396111
2022 Structural Characterization of KOR Inactive and Active States for 3D Pharmacology and Drug Discovery. Handbook of experimental pharmacology 2 33945028
2021 Estimation of ZYKR1 in human urine and plasma utilizing LC-MS/MS positive electrospray ionization; a kappa opioid receptor (KOR) agonist. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 2 34731743
2012 An efficient synthesis of 3-OBn-6β,14-epoxy-bridged opiates from naltrexone and identification of a related dual MOR inverse agonist/KOR agonist. Bioorganic & medicinal chemistry letters 2 22771010
2025 Triazole 187 is a biased KOR agonist that suppresses itch without sedation and induces anxiolytic-like behaviors in mice. bioRxiv : the preprint server for biology 1 40027836
2025 The efficacy and safety of kappa opioid receptor (KOR) agonists in patients with uraemic pruritus: a systematic review and network meta-analysis. Clinical kidney journal 1 40567495
2024 Decoding the κ Opioid Receptor (KOR): Advancements in Structural Understanding and Implications for Opioid Analgesic Development. Molecules (Basel, Switzerland) 1 38893511
2023 [Polymorphisms of OPRM1, OPRK1, DCC genes and non-suicidal self-injuries in adults]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova 1 38147391