Affinage

OPRK1

Kappa-type opioid receptor · UniProt P41145

Length
380 aa
Mass
42.6 kDa
Annotated
2026-06-10
100 papers in source corpus 21 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

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 that operates across pain modulation, aversion/reward circuits, and stress-driven behavior (PMID:17005613, PMID:32057802). Agonist occupancy drives phosphorylation at the C-terminal tail by GRK as the initiating step of β-arrestin-dependent desensitization, and downstream KOR activation increases ERK1/2 and p38 MAPK phosphorylation, with p38 in turn phosphorylating the KIR3.1 (GIRK1) channel (PMID:21370032); KOR-dependent ERK1/2 signaling is also functional in immune cells (PMID:22424981). Site-specific knockin of four C-terminal phospho-sites establishes that this phosphorylation governs U50,488H tolerance and conditioned place aversion in a sex-dependent manner, attenuating tolerance in males and preventing aversion in females (PMID:34736959). Peripheral analgesic signaling requires adenylyl cyclase 3 in DRG neurons, where KOR inhibits voltage-gated potassium channels (PMID:34914639). In neural circuits, KOR is expressed on GABAergic OFF/NEUTRAL cells of the rostral ventromedial medulla (PMID:17005613), on insular GABAergic neurons where it gates pain-related aversive memory (PMID:37679857), and within the mesolimbic system, where VTA KOR activation is necessary for aversion-induced dopamine suppression and avoidance learning (PMID:32057802) and KOR overexpression in VTA dopaminergic neurons recapitulates alcohol dependence phenotypes (PMID:36764577). Crystallographic structures of inactive (JDTic-bound) and active KOR have defined ligand-binding determinants and enabled structure-based ligand discovery (PMID:33945028). Beyond neural function, OPRK1 is transcriptionally repressed by androgen receptor binding at its promoter, and upon AR-inhibitor-driven de-repression interacts with SLC9A3R1 to promote autophagic degradation of REST and neuroendocrine differentiation in prostate cancer (PMID:41353213); its expression is also modulated by an upstream regulatory indel and by promoter CpG methylation (PMID:18319328, PMID:26300544).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1999 Medium

    Established that distinct kappa agonists engage non-equivalent receptor mechanisms, raising the question of how a single locus produces multiple analgesic pathways.

    Evidence Exon-specific antisense oligodeoxynucleotide knockdown of KOR-1 with multiple ligands in an in vivo analgesia assay

    PMID:10224306

    Open questions at the time
    • Splice variants/conformations not molecularly defined
    • Single lab, antisense specificity not genetically confirmed
  2. 2006 Medium

    Resolved which RVM cell types carry KOR, showing KOR marks GABAergic OFF/NEUTRAL pain-modulating neurons rather than ON cells.

    Evidence Electrophysiological cell classification with juxtacellular labeling and KOR/GAD67 immunofluorescence co-labeling

    PMID:17005613

    Open questions at the time
    • Functional consequence of KOR activation on these cells not directly tested here
    • Circuit output not measured
  3. 2008 Medium

    Identified a functional cis-regulatory determinant of OPRK1 expression, addressing how receptor levels are set.

    Evidence Luciferase promoter assay of an upstream indel plus family-based genotyping

    PMID:18319328

    Open questions at the time
    • Endogenous chromatin effect not shown
    • Transcription factors binding the indel not identified
  4. 2011 Medium

    Defined the KOR desensitization initiation step and downstream kinase cascade, linking C-terminal phosphorylation to β-arrestin recruitment and effector channel modulation.

    Evidence Phospho-selective antibody immunohistochemistry at Ser369 with behavioral stress validation; readouts of ERK1/2, p38, and KIR3.1 phosphorylation

    PMID:21370032

    Open questions at the time
    • β-arrestin recruitment not directly measured here
    • Stoichiometry of multi-site phosphorylation unresolved
  5. 2012 Medium

    Demonstrated KOR is a functional signaling receptor on immune cells, extending its role beyond neurons.

    Evidence Dynorphin A(1-17) vs inactive A(2-17) stimulation of phospho-ERK1/2 in J774 macrophages by Western blot

    PMID:22424981

    Open questions at the time
    • Physiological immune consequence not established
    • G protein coupling in this context not dissected
  6. 2015 High

    Established the limits of dynorphin and 'KOR-selective' ligand specificity using genetic knockouts, a critical caveat for interpreting KOR pharmacology.

    Evidence [35S]GTPγS binding in striatal membranes from WT, KOR-KO, and MOR-KO mice

    PMID:26160155

    Open questions at the time
    • Identity of the additional dynorphin-coupled G proteins not defined
    • Restricted to striatal tissue
  7. 2015 Medium

    Mapped endogenous KOR-expressing cell populations across brain and peripheral tissues, providing a genetic substrate for circuit dissection.

    Evidence KOR-Cre knockin mouse with reporter recombination and histology

    PMID:26575788

    Open questions at the time
    • Cre knockin disrupts coding sequence (potential haploinsufficiency)
    • Expression timing/level not quantified per cell
  8. 2016 Low

    Linked OPRK1 promoter methylation to expression and to demographic variables, addressing epigenetic regulation of the receptor.

    Evidence Bisulfite pyrosequencing and dual-luciferase reporter assays in two populations

    PMID:26300544 PMID:27838450

    Open questions at the time
    • No mutagenesis confirming methylation-mediated silencing mechanism
    • Reporter assays without endogenous validation
  9. 2020 Medium

    Established that VTA KOR activation is necessary for aversion-induced dopamine suppression and avoidance learning, placing KOR causally in mesolimbic aversion encoding.

    Evidence Intra-VTA KOR antagonist microinjection with real-time voltammetric dopamine measurement and behavioral avoidance testing in rats

    PMID:32057802

    Open questions at the time
    • Pre/postsynaptic site of KOR action within VTA not resolved
    • Single lab
  10. 2021 High

    Proved C-terminal phosphorylation governs tolerance and aversion in a sex-dependent manner, dissociating these from acute receptor effects.

    Evidence K4A phosphorylation-deficient knockin mice with behavioral assays and receptor binding autoradiography

    PMID:34736959

    Open questions at the time
    • Molecular basis of sex dependence unknown
    • Specific arrestin/kinase mediating each behavior not assigned
  11. 2022 High

    Identified peripheral AC3 as required for KOR analgesia and Kv-channel inhibition, refining the effector requirements of KOR signaling.

    Evidence Conditional AC3 KO in DRG with patch-clamp, cAMP, behavior, and AC1-inhibitor rescue

    PMID:34914639

    Open questions at the time
    • Whether AC3 acts via classical Gαi/o or direct KOR–AC3 interaction not distinguished
    • Central analgesic mechanisms not addressed
  12. 2022 Medium

    Dissociated central diuretic from peripheral electrolyte-retaining KOR effects on renal function.

    Evidence Route-specific (ICV vs IV) norBNI pretreatment with urine/electrolyte measurement in rats

    PMID:36202183

    Open questions at the time
    • Specific central and peripheral KOR sites not identified
    • Downstream renal signaling unknown
  13. 2022 Medium

    Showed KOR within kisspeptin neurons is dispensable for GnRH/LH pulse generation and fertility, a well-controlled negative result for KOR's reproductive role.

    Evidence Conditional Oprk1 KO in kisspeptin neurons with LH pulse monitoring, hormone assays, and fertility assessment

    PMID:36260530

    Open questions at the time
    • KOR action on other hypothalamic populations not excluded
    • Compensation by other opioid receptors not tested
  14. 2022 High

    Consolidated structural understanding of KOR activation and selectivity, enabling rational ligand discovery.

    Evidence X-ray crystallography of KOR-JDTic and active-state structures with structure-based virtual screening

    PMID:33945028

    Open questions at the time
    • G protein/arrestin-coupled state-specific dynamics not fully captured here
    • Biased-signaling structural determinants not resolved
  15. 2023 Low

    Identified the BLA(KOR)→BNST circuit through which the dynorphin/KOR system regulates stress-escalated alcohol consumption.

    Evidence DREADD chemogenetics in Oprk1-Cre mice with circuit-specific norBNI and two-bottle choice after social defeat (preprint)

    PMID:39574601

    Open questions at the time
    • Preprint, not peer-reviewed
    • Endogenous dynorphin source onto this circuit not defined
  16. 2023 Medium

    Established VTA dopaminergic KOR overexpression as causally sufficient to produce alcohol dependence phenotypes, and placed KOR upstream of insular GABAergic control of pain-aversive memory.

    Evidence Cre-Lox Oprk1 overexpression in VTA DA neurons with alcohol self-administration; pharmacological KOR manipulation plus GABAergic DREADDs in insular cortex

    PMID:36764577 PMID:37679857

    Open questions at the time
    • Overexpression may exceed physiological KOR levels
    • Synaptic mechanism of KOR-GABAergic inhibition not detailed
  17. 2023 Medium

    Defined a non-neural OPRK1 axis in cancer: AR represses OPRK1, and de-repressed OPRK1 drives REST autophagic degradation via SLC9A3R1 to induce neuroendocrine differentiation.

    Evidence AR ChIP at OPRK1 promoter, OPRK1–SLC9A3R1 co-IP, autophagy flux, REST Western blot, and pharmacological rescue in prostate cancer

    PMID:41353213

    Open questions at the time
    • Direct GPCR signaling contribution vs scaffold role of OPRK1 not separated
    • Single lab, reciprocal co-IP validation not detailed

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how KOR distinguishes among its diverse ligand-, circuit-, and tissue-specific outputs at the molecular level, including the structural basis of biased signaling and the determinants of sex-dependent behavioral effects.
  • No structural model of biased agonism linked to behavior
  • Molecular basis of sex-dependent phosphorylation effects unknown
  • G protein/effector selectivity across tissues not unified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0048018 receptor ligand activity 2
Localization
GO:0005886 plasma membrane 2
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 3
Partners
AC3SLC9A3R1

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 presence of the 830 bp insertion reduces transcriptional activity by approximately half in transient transfection promoter assays, establishing this indel as a functional regulatory variation affecting OPRK1 expression. Transient transfection promoter assay (luciferase reporter), PCR-based genotyping, family-based association analysis Human molecular genetics Medium 18319328
2015 OPRK1 promoter CpG methylation suppresses OPRK1 gene expression; a CpGs-containing fragment of the OPRK1 promoter significantly increased reporter gene expression in luciferase assays, indicating that hypermethylation of this region reduces OPRK1 transcription. Bisulfite pyrosequencing for methylation quantification; luciferase reporter assay Neuroscience letters Low 26300544
2016 OPRK1 promoter fragments also drive reporter gene expression in a dual-luciferase assay (replicated in a second study population), and OPRK1 promoter methylation is positively correlated with gender, ethnicity, and aging. Bisulfite pyrosequencing; dual-luciferase reporter gene assay Neuroscience letters Low 27838450
2006 KOR (OPRK1 protein) immunoreactivity is present in the majority of OFF and NEUTRAL cells (86% and 80%, respectively) but rarely in ON cells (13%) in the rostral ventromedial medulla (RVM); most KOR-immunoreactive cells co-express GAD67, identifying them as GABAergic neurons, supporting direct KOR-mediated inhibition of these pain-modulating cell types. Extracellular neuronal recording, juxtacellular labeling with biotinamide, immunofluorescence co-labeling for KOR and GAD67 Journal of neurophysiology Medium 17005613
2012 KOR expressed on murine macrophage J774 cells is functionally active: ligation with dynorphin A(1-17) triggers ERK1/2 phosphorylation, whereas the truncated dynorphin A(2-17) (which does not bind KOR) was ineffective, demonstrating KOR-dependent ERK1/2 signaling in immune cells. FACS, immunocytochemistry, Western blot for phospho-ERK1/2, IFN-γ stimulation, dynorphin ligand pharmacology Journal of neuroimmunology Medium 22424981
2011 Agonist-activated KOR is phosphorylated at Ser369 in its C-terminal tail by G protein-coupled receptor kinase (GRK), which constitutes the first step in β-arrestin-dependent KOR desensitization; downstream KOR activation increases phosphorylation of both ERK1/2 and p38 MAP kinase, and p38 MAP kinase phosphorylates KIR3.1 (GIRK1) channel. Phospho-selective antibody immunohistochemistry, validated in behavioral stress models Methods in molecular biology Medium 21370032
2021 Agonist-promoted phosphorylation of mouse KOR at four C-terminal residues (mutated to Ala in K4A knockin mice) plays a sex-dependent role in U50,488H-induced tolerance and conditioned place aversion (CPA): abolishing phosphorylation attenuated tolerance in males but not females, and prevented CPA in females but not males, without affecting acute anti-pruritic or hypo-locomotor effects. K4A knockin mouse line generation, autoradiography ([3H]U69,593 binding), behavioral assays (scratching, locomotion, CPA, tolerance), Western blot Neuropharmacology High 34736959
1999 Antisense oligodeoxynucleotide mapping of KOR-1 (OPRK1) exons revealed that dynorphin B and alpha-neoendorphin analgesia uses a different receptor mechanism than U50,488H analgesia despite all being norBNI-reversible: probes targeting exon 1 or 2 blocked U50,488H but not dynorphin B/alpha-neoendorphin analgesia, indicating multiple kappa analgesic mechanisms dependent on distinct receptor splice variants or conformations. Antisense oligodeoxynucleotide knockdown of specific KOR-1 exons, in vivo analgesia assay, radioligand binding Brain research Medium 10224306
2015 In striatal membranes from KOR knockout mice, dynorphin peptides (but not U69,593) retain full potency and efficacy in stimulating [35S]GTPγS binding, demonstrating that dynorphin promiscuously activates multiple G proteins beyond KOR in striatum; furthermore, norBNI and 5'GNTI maintain full antagonist potency in KOR-KO mice, revealing that these commonly used 'KOR-selective' antagonists are nonselective in an endogenous tissue context. [35S]GTPγS binding assay in striatal membrane preparations from WT, KOR-KO, and MOR-KO mice Neuropharmacology High 26160155
2022 Conditional knockout of adenylyl cyclase 3 (AC3) in DRG neurons eliminated KOR agonist-induced analgesia and KOR-mediated inhibition of voltage-gated potassium (Kv) channels, demonstrating that peripheral AC3 is required for KOR opioid analgesia through either classical Gαi/o signaling or direct KOR–AC3 protein interaction. Conditional KO of AC3 in L3/L4 DRGs, patch-clamp electrophysiology (Kv currents), behavioral nociception assays, Western blot, cAMP measurement, pharmacological rescue with AC1 inhibitor JCI insight High 34914639
2022 The crystal structure of human KOR in complex with the antagonist JDTic (solved in 2012) and a subsequently determined active-state KOR structure provided atomistic insight into subtype selectivity and activation mechanisms; structure-based virtual screening from these structures has enabled discovery of new KOR-selective ligands. X-ray crystallography (KOR-JDTic complex); structure-based virtual screening Handbook of experimental pharmacology High 33945028
2020 Blockade of KOR in the ventral tegmental area (VTA) attenuated aversion-induced reductions in dopamine in the nucleus accumbens and prevented learned avoidance behavior, demonstrating that VTA KOR activation is necessary for aversion-induced dopamine suppression and the encoding of avoidance. Intra-VTA KOR antagonist microinjection, real-time voltammetric dopamine measurement, behavioral avoidance testing in rats Neuropharmacology Medium 32057802
2023 Overexpression of Oprk1 in VTA dopaminergic neurons (TH::Cre rats) recapitulated phenotypes of alcohol dependence including escalated alcohol self-administration and depressive-like behavior, establishing that KOR signaling within the mesolimbic dopamine system causally contributes to these alcohol dependence phenotypes. Cre-Lox conditional Oprk1 overexpression in VTA DA neurons (TH::Cre rats), operant alcohol self-administration, sucrose preference, behavioral assays Neuropharmacology Medium 36764577
2022 Conditional deletion of KOR specifically from kisspeptin neurons (KNDy neurons) did not alter LH pulse parameters, puberty, estrous cycles, FSH levels, LH surges, or fertility in male or female mice, demonstrating that KOR signaling within kisspeptin neurons is not strictly required for normal GnRH/LH pulse generation. Conditional Oprk1 knockout in kisspeptin neurons (Kiss1-Cre × Oprk1flox/flox), in vivo LH pulse monitoring, hormonal measurements, fertility assessments Endocrinology Medium 36260530
2023 OPRK1 is transcriptionally repressed by androgen receptor (AR) binding to its promoter; AR pathway inhibitors (ARPIs) de-repress OPRK1, leading to upregulation of OPRK1 protein. Elevated OPRK1 then interacts with SLC9A3R1, promoting autophagic degradation of the transcriptional repressor REST and thereby inducing neuroendocrine differentiation in prostate cancer. AR ChIP at OPRK1 promoter, co-immunoprecipitation (OPRK1–SLC9A3R1), autophagy flux assays, REST protein levels by Western blot, neuroendocrine marker expression, pharmacological rescue (JTC-801 + chloroquine) Cell death & disease Medium 41353213
2023 Activation of KOR in the insular cortex blocked pain-related aversive memory behaviors, whereas KOR inhibition induced such behaviors; chemogenetic activation of GABAergic neurons reversed the effect of KOR activation, placing KOR upstream of (and inhibitory to) insular GABAergic neuron activity in the circuit controlling pain-related aversive memory. Pharmacological KOR agonism/antagonism in insular cortex, DREADD chemogenetics of GABAergic neurons, behavioral fear/aversive memory assays Cerebral cortex Medium 37679857
2022 Nalfurafine (KOR agonist) produces diuresis and antinatriuresis; this diuretic effect is mediated through central KOR pathways (blocked by ICV but not IV norBNI pretreatment), while the electrolyte-retaining effects occur via peripheral KOR pathways, dissociating central and peripheral mechanisms of KOR-mediated renal function. ICV vs IV norBNI pretreatment in conscious catheterized rats, urine output and electrolyte measurements Pharmacological research Medium 36202183
2023 KOR activation in ER-positive breast cancer cells (MCF-7, T47D) inhibited cellular proliferation and promoted apoptosis; downstream pathway analysis and XBP1 silencing experiments established that the anti-tumor effect operates through a KOR-ER-XBP1 signaling axis. KOR agonist treatment of ER+ breast cancer cell lines, proliferation and apoptosis assays, siRNA knockdown of XBP1, GO/KEGG pathway analysis, PPI network analysis Biomedicine & pharmacotherapy Low 37708692
2022 Famotidine was identified as a drug that directly binds KOR (by structure-based virtual screening and binding validation) and promotes oligodendrocyte precursor cell (OPC) maturation and CNS remyelination through KOR/STAT3 signaling pathway. Structure-based virtual screening, in vitro OPC differentiation assays, in vivo remyelination model, STAT3 pathway analysis International journal of biological macromolecules Low 38692525
2024 Chemogenetic activation of KOR-expressing neurons in the basolateral amygdala (BLAKORs) and their projections to the BNST attenuated social stress-escalated alcohol consumption in both male and female mice, identifying the BLAKOR→BNST circuit as a specific pathway through which the dynorphin/KOR system regulates stress-induced alcohol drinking. DREADD chemogenetics in Oprk1-Cre mice (BLA-specific), systemic and BNST-specific KOR antagonism (norBNI), two-bottle choice alcohol consumption after repeated social defeat stress bioRxivpreprint Low 39574601
2015 A KOR-Cre knockin mouse was generated in which Cre recombinase replaces the initial coding sequence of Oprk1; the allele mediates recombination by E14.5 and is expressed in cerebral cortex, nucleus accumbens, striatum, heart, lung, liver, and retinal bipolar/amacrine cells, providing a genetic map of KOR-expressing cell populations. Knockin mouse generation, Cre-reporter recombination assays, histological characterization across tissues and brain regions Genesis Medium 26575788

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 64 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 53 8366038
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 52 35069503
2008 A regulatory variation in OPRK1, the gene encoding the kappa-opioid receptor, is associated with alcohol dependence. Human molecular genetics 51 18319328
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 32 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 Synthesis of mixed MOR/KOR efficacy cyclic opioid peptide analogs with antinociceptive activity after systemic administration. European journal of medicinal chemistry 28 26785295
2011 Oral infection with Porphyromonas gingivalis and systemic cytokine profile in C57BL/6.KOR-ApoE shl mice. Journal of periodontal research 28 22097957
2015 OPRK1 promoter hypermethylation increases the risk of Alzheimer's disease. Neuroscience letters 27 26300544
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
2015 Generation of a KOR-Cre knockin mouse strain to study cells involved in kappa opioid signaling. Genesis (New York, N.Y. : 2000) 24 26575788
1984 Involvement of kil and kor genes in the phenotype of a host-range mutant of RP4. Molecular & general genetics : MGG 24 6097793
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
2020 Modulation of cocaine-related behaviors by low doses of the potent KOR agonist nalfurafine in male C57BL6 mice. Psychopharmacology 18 32435819
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
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
2021 Agonist-promoted kappa opioid receptor (KOR) phosphorylation has behavioral endpoint-dependent and sex-specific effects. Neuropharmacology 14 34736959
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
1999 Antisense mapping KOR-1: evidence for multiple kappa analgesic mechanisms. Brain research 14 10224306
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
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
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) 11 37679857
2017 Molecular identification of the Dyn/Kor system and its potential role in the reproductive axis of goldfish. General and comparative endocrinology 11 28242307
2022 Conditional Deletion of KOR (Oprk1) in Kisspeptin Cells Does Not Alter LH Pulses, Puberty, or Fertility in Mice. Endocrinology 10 36260530
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
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
2018 Isolation and characterization of a new Methanoculleus bourgensis strain KOR-2 from the rumen of Holstein steers. Asian-Australasian journal of animal sciences 7 30056662
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
2022 Difelikefalin, a peripherally restricted KOR (kappa opioid receptor) agonist, produces diuresis through a central KOR pathway. Pharmacological research 6 36202183
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
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 Selective KOR antagonist alters functional patch sizes in individualized brain system: results from the Fast-fail Trial in Mood and Anxiety Spectrum Disorders (FAST-MAS). Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 2 40360690
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 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
2025 OPRK1 drives SLC9A3R1 progression to neuroendocrine prostate cancer. Cell death & disease 1 41353213
2024 Decoding the κ Opioid Receptor (KOR): Advancements in Structural Understanding and Implications for Opioid Analgesic Development. Molecules (Basel, Switzerland) 1 38893511
2024 BLAKOR inputs to the BNST regulate social stress-escalated alcohol consumption. bioRxiv : the preprint server for biology 1 39574601
2023 [Polymorphisms of OPRM1, OPRK1, DCC genes and non-suicidal self-injuries in adults]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova 1 38147391

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