Nomenclature: κ receptor

Family: Opioid receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates. 

Contents

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 380 8q11.2 OPRK1 opioid receptor, kappa 1 51,84,106
Mouse 7 380 1 A2-A3 Oprk1 opioid receptor, kappa 1 6,37,47,62,102
Rat 7 380 5q11 Oprk1 opioid receptor, kappa 1 12,46,53-54,61
Previous and Unofficial Names
KOP
KOR-1
Kappa opioid receptor
OP2
KOR
K-OR-1
kappa-type opioid receptor
opioid receptor, kappa 1
Oprk2
R21
KOP-r
Database Links
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GPCRDB
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the human kappa opioid receptor in complex with JDTic
PDB Id:  4DJH
Ligand:  JDTic
Resolution:  2.9Å
Species:  Human
References:  101
Natural/Endogenous Ligands
α-neoendorphin {Sp: Human, Mouse, Rat}
β-endorphin {Sp: Rat} , β-endorphin {Sp: Human} , β-endorphin {Sp: Mouse}
β-neoendorphin {Sp: Human, Mouse, Rat}
big dynorphin {Sp: Human, Mouse, Rat}
dynorphin A {Sp: Human, Mouse, Rat}
dynorphin A-(1-13) {Sp: Human, Mouse, Rat}
dynorphin A-(1-8) {Sp: Human, Mouse, Rat}
dynorphin B {Sp: Human, Mouse, Rat}
[Leu]enkephalin {Sp: Human, Mouse, Rat}
[Met]enkephalin {Sp: Human, Mouse, Rat}
Comments: dynorphin A and big dynorphin are the highest potency endogenous ligands
Principal endogenous agonists (Human)
big dynorphin (PDYN, P01213), dynorphin A (PDYN, P01213)
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
nalfurafine Hs Full agonist 10.1 pKd 99
pKd 10.1 [99]
EKC Hs Full agonist 9.4 pKd 107
pKd 9.4 [107]
enadoline Hs Full agonist 8.6 – 9.2 pKd 26
pKd 8.6 – 9.2 [26]
[3H]U69593 Hs Full agonist 8.7 – 8.8 pKd 40,66,84
pKd 8.7 – 8.8 (Kd 2x10-9 – 1.6x10-9 M) [40,66,84]
(-)-bremazocine Hs Partial agonist 10.5 pKi 94
pKi 10.5 [94]
dynorphin A {Sp: Human, Mouse, Rat} Rn Full agonist 10.0 – 10.3 pKi 46,53
pKi 10.0 – 10.3 [46,53]
(-)-cyclazocine Hs Partial agonist 10.0 pKi 94
pKi 10.0 [94]
(-)-EKC Hs Full agonist 10.0 pKi 94
pKi 10.0 [94]
dynorphin A-(1-13) {Sp: Human, Mouse, Rat} Hs Full agonist 9.3 – 10.7 pKi 66,94
pKi 9.3 – 10.7 [66,94]
dynorphin A-(1-13) {Sp: Human, Mouse, Rat} Rn Full agonist 9.9 pKi 53
pKi 9.9 [53]
U63640 Rn Full agonist 9.7 pKi 53
pKi 9.7 [53]
etorphine Hs Full agonist 9.7 pKi 94
pKi 9.7 [94]
dynorphin-(1-11) Hs Full agonist 9.7 pKi 94
pKi 9.7 [94]
GR 89696 Hs Full agonist 9.7 pKi 72
pKi 9.7 [72]
enadoline Hs Full agonist 9.6 pKi 31,59
pKi 9.6 [31,59]
dynorphin A {Sp: Human, Mouse, Rat} Hs Full agonist 8.3 – 10.8 pKi 66,84,94,106-107
pKi 8.3 – 10.8 [66,84,94,106-107]
naloxone benzoylhydrazone Hs Partial agonist 9.5 pKi 94
pKi 9.5 [94]
dynorphin B {Sp: Human, Mouse, Rat} Rn Full agonist 9.5 pKi 53
pKi 9.5 [53]
U69593 Hs Full agonist 9.5 pKi 40,94
pKi 9.5 [40,94]
α-neoendorphin {Sp: Human, Mouse, Rat} Rn Full agonist 8.9 – 10.0 pKi 46,53
pKi 8.9 – 10.0 [46,53]
α-neoendorphin {Sp: Human, Mouse, Rat} Hs Full agonist 8.3 – 10.2 pKi 84,106
pKi 8.3 – 10.2 [84,106]
E2078 Hs Full agonist 9.1 pKi 73
pKi 9.1 [73]
β-neoendorphin {Sp: Human, Mouse, Rat} Rn Full agonist 9.1 pKi 53
pKi 9.1 [53]
spiradoline Rn Full agonist 9.0 pKi 12
pKi 9.0 [12]
dynorphin B {Sp: Human, Mouse, Rat} Hs Partial agonist 8.1 – 9.9 pKi 66,84,94
pKi 8.1 – 9.9 [66,84,94]
dynorphin A-(1-8) {Sp: Human, Mouse, Rat} Hs Full agonist 8.0 – 9.9 pKi 66,84,94,103
pKi 8.0 – 9.9 [66,84,94,103]
E2078 Rn Full agonist 8.8 pKi 53
pKi 8.8 [53]
ICI 204448 Rn Full agonist 8.8 pKi 12
pKi 8.8 [12]
EKC Rn Full agonist 8.8 pKi 53
pKi 8.8 [53]
tifluadom Hs Full agonist 8.8 pKi 107
pKi 8.8 [107]
U50488 Hs Agonist 7.8 – 9.7 pKi 11,66,84,94,98,106-107
pKi 7.8 – 9.7 [11,66,84,94,98,106-107]
hydromorphone Hs Agonist 8.55 pKi 100
pKi 8.55 (Ki 2.8x10-9 M) [100]
nalorphine Hs Partial agonist 7.9 – 9.1 pKi 94,107
pKi 7.9 – 9.1 [94,107]
U50488 Rn Partial agonist 8.2 – 8.7 pKi 12,46,53
pKi 8.2 – 8.7 [12,46,53]
U69593 Rn Full agonist 8.0 – 8.7 pKi 12,53
pKi 8.0 – 8.7 [12,53]
salvinorin A Hs Full agonist 7.8 – 8.7 pKi 9,76
pKi 7.8 – 8.7 [9,76]
(-)-pentazocine Hs Partial agonist 7.8 – 8.6 pKi 94,107
pKi 7.8 – 8.6 [94,107]
β-neoendorphin {Sp: Human, Mouse, Rat} Hs Full agonist 7.9 pKi 84
pKi 7.9 [84]
normorphine Hs Full agonist 7.8 pKi 94
pKi 7.8 [94]
nalbuphine Hs Full agonist 7.4 – 7.5 pKi 107
pKi 7.4 – 7.5 [107]
morphine Hs Partial agonist 7.3 pKi 94
pKi 7.3 [94]
β-endorphin {Sp: Human} Hs Partial agonist 6.3 – 7.9 pKi 84,94
pKi 6.3 – 7.9 [84,94]
fentanyl Hs Partial agonist 7.1 pKi 94
pKi 7.1 [94]
dihydromorphine Hs Partial agonist 7.1 pKi 94
pKi 7.1 [94]
etonitazene Hs Partial agonist 6.9 pKi 94
pKi 6.9 [94]
morphine Rn Partial agonist 6.7 – 7.0 pKi 12,53
pKi 6.7 – 7.0 [12,53]
β-endorphin {Sp: Human} Rn Full agonist 6.8 pKi 53
pKi 6.8 [53]
hydrocodone Hs Agonist 6.59 pKi 60
pKi 6.59 (Ki 2.6x10-7 M) [60]
(-)-methadone Hs Partial agonist 6.5 pKi 94
pKi 6.5 [94]
DAMGO Hs Partial agonist 6.5 pKi 94
pKi 6.5 [94]
[Leu]enkephalin {Sp: Human, Mouse, Rat} Rn Full agonist 6.0 pKi 53
pKi 6.0 [53]
[Met]enkephalin {Sp: Human, Mouse, Rat} Rn Full agonist 6.0 pKi 53
pKi 6.0 [53]
DAMGO Rn Partial agonist 5.9 pKi 53
pKi 5.9 [53]
α-neoendorphin {Sp: Human, Mouse, Rat} Mm Full agonist 10.0 pIC50 102
pIC50 10.0 [102]
dynorphin B {Sp: Human, Mouse, Rat} Mm Full agonist 10.0 pIC50 102
pIC50 10.0 [102]
[D-Ala2,F5,Phe4]dynorphin-(1-17)-NH2 Mm Full agonist 9.7 pIC50 102
pIC50 9.7 [102]
dynorphin-(1-17)-NH2 Mm Full agonist 9.7 pIC50 102
pIC50 9.7 [102]
dynorphin A-(1-8) {Sp: Human, Mouse, Rat} Mm Full agonist 9.7 pIC50 102
pIC50 9.7 [102]
(-)-bremazocine Mm Full agonist 9.5 pIC50 102
pIC50 9.5 [102]
dynorphin A {Sp: Human, Mouse, Rat} Mm Full agonist 9.4 pIC50 102
pIC50 9.4 [102]
[Met5]dynorphin-(1-17) Mm Full agonist 9.2 pIC50 102
pIC50 9.2 [102]
spiradoline Mm Full agonist 9.0 pIC50 102
pIC50 9.0 [102]
U50488 Mm Partial agonist 9.0 pIC50 102
pIC50 9.0 [102]
EKC Mm Full agonist 9.0 pIC50 102
pIC50 9.0 [102]
U69593 Mm Full agonist 8.6 pIC50 102
pIC50 8.6 [102]
ICI 204448 Mm Full agonist 8.2 pIC50 102
pIC50 8.2 [102]
[D-Ala2,F5,Phe4]dynorphin-(1-13)-NH2 Mm Full agonist 7.7 pIC50 102
pIC50 7.7 [102]
β-endorphin {Sp: Human} Mm Partial agonist 7.4 pIC50 102
pIC50 7.4 [102]
nalbuphine Mm Full agonist 7.4 pIC50 102
pIC50 7.4 [102]
meperidine Hs Agonist 5.63 pIC50 71
pIC50 5.63 (IC50 2.37x10-6 M) [71]
View species-specific agonist tables
Agonist Comments
Ki values were determined in the absence of Na+ and GDP, except TRK820.

Discrimination of full or partial agonism is very dependent on the level of receptor expression and on the assay used to monitor agonist effects. Many agents may behave as full agonists or potent partial agonists in cell lines expressing cloned receptors in high concentration, but in other environments they may show only weak agonist activity. The identification of agonist activity in the table is largely based on the ability to stimulate GTPγS binding in cell lines expressing cloned human kappa receptors. Agents giving 85% or greater stimulation than that given by U69593 have been characterized as Full Agonists [94].

κ opioid receptors have been divided into several different subtypes, mainly on the basis of [3H]agonist binding assays. Generally 2 subtypes are recognised: κ1 and κ2. The benzeneacetamides and peptides are considered κ1 agonists and the benzomorphans bind to κ1 and κ2. However, there is only one gene product and the subtypes are considered putative.

Selective κ agonists are of several structural types. All have high affinity for the κ receptor and are full agonists.
We have tagged the μ receptor as the primary drug target for hydrocodone based on this drug having the highest affinity at this receptor compared to the κ and δ receptors [60]. Similarly, we have tagged the μ receptor as the primary target of the drug hydromorphone[100].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H]diprenorphine Hs Antagonist 9.1 pKd 84
pKd 9.1 [84]
nor-binaltorphimine Rn Antagonist 9.6 – 10.7 pKi 12,46,53
pKi 9.6 – 10.7 [12,46,53]
nor-binaltorphimine Hs Antagonist 8.9 – 11.0 pKi 66,70,84,94,106-107
pKi 8.9 – 11.0 [66,70,84,94,106-107]
GNTI Hs Antagonist 9.74 – 9.9 pKi 32,66,89
pKi 9.74 – 9.9 [32,66,89]
β-FNA Hs Antagonist 9.7 pKi 94
pKi 9.7 [94]
quadazocine Hs Antagonist 9.7 pKi 94
pKi 9.7 [94]
buprenorphine Hs Antagonist 9.1 – 10.2 pKi 94,107
pKi 9.1 – 10.2 [94,107]
diprenorphine Hs Antagonist 9.6 – 9.7 pKi 66,94,106-107
pKi 9.6 – 9.7 [66,94,106-107]
nalmefene Hs Antagonist 9.5 pKi 94
pKi 9.5 [94]
naltrexone Hs Antagonist 8.4 – 9.4 pKi 66,84,94
pKi 8.4 – 9.4 [66,84,94]
naltriben Hs Antagonist 8.4 pKi 94
pKi 8.4 [94]
BNTX Hs Antagonist 8.4 pKi 94
pKi 8.4 [94]
naloxone Hs Antagonist 7.6 – 8.6 pKi 66,84,94,106-107
pKi 7.6 – 8.6 [66,84,94,106-107]
naltrindole Hs Antagonist 8.0 pKi 94
pKi 8.0 [94]
naltrindole Rn Antagonist 7.9 pKi 46
pKi 7.9 [46]
naloxone Rn Antagonist 7.7 – 8.0 pKi 12,46,53
pKi 7.7 – 8.0 [12,46,53]
alvimopan Hs Antagonist 7.0 pKi 43
pKi 7.0 (Ki 1x10-7 M) [43]
(+)-naloxone Rn Antagonist 4.7 pKi 53
pKi 4.7 [53]
naltrexone Mm Antagonist 9.2 pIC50 102
pIC50 9.2 [102]
nor-binaltorphimine Mm Antagonist 8.9 pIC50 102
pIC50 8.9 [102]
naloxone Mm Antagonist 8.3 pIC50 102
pIC50 8.3 [102]
naltrindole Mm Antagonist 7.4 pIC50 102
pIC50 7.4 [102]
View species-specific antagonist tables
Allosteric Modulator Comments
Although no small molecules are considered direct allosteric regulators of κ opioid receptors, a number of proteins such as G protein-coupled receptor kinases, β-arrestins and G proteins clearly regulate receptor affinities and function. Furthermore, sodium and guanine nucleotides can modify the functional κ receptor complex and G protein interaction. Also, other G protein-coupled receptors appear to be able to form heterodimers with κ receptors, potentially modifying κ opioid receptor activity.
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
Potassium channel
Calcium channel
References:  4,23,25,36,42,55,80,90
Secondary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family
G12/G13 family
Adenylate cyclase inhibition
Phospholipase C stimulation
Other - See Comments
Comments:  Activation of κ opioid receptors stimulates p42/p44 MAP kinase via βγ subunits of Gi/o proteins [8].
κ opioid receptors interact with NHERF-1/EBP50 to stimulate Na+/H+ exchange independent of Gi/o proteins [30].
References:  8,30,41,45,57,96
Tissue Distribution
Skin.
Species:  Human
Technique:  RT-PCR and Immunohistochemistry.
References:  78
CNS: olfactory bulb, nucleus accumbens, caudate nucleus, putamen, temporal cortex, parietal cortex, thalamic nuclei > amygdala, occipital cortex, frontal cortex, hypothalamus, ventral tegmental area, cerebellar cortex > hippocampus, corpus mamillare, locus coeruleus, pituitary, spinal cord > globus pallidus, substantia nigra, superior colliculus, inferior colliculus, olivary nucleus.
Species:  Human
Technique:  RT-PCR.
References:  84
CNS: amygdala, caudate nucleus, hypothalamus, subthalamic nucleus > hippocampus, thalamus > substantia nigra, corpus callosum.
Species:  Human
Technique:  Northern blotting.
References:  106
Immune cells.
Species:  Human
Technique:  RT-PCR.
References:  19
CNS: claustrum, nucleus accumbens, endopiriform nucleus, ventral pallidum, preoptic area, fundus striati, hypothalamus, substantia nigra.
Species:  Mouse
Technique:  Radioligand binding.
References:  35
CNS: olfactory tubercle, endopiriform nucleus, ventral pallidum, hypothalamus, deep cortical layers, claustrum.
Species:  Mouse
Technique:  Radioligand binding.
References:  35
Intestine.
Species:  Mouse
Technique:  RT-PCR.
References:  69
Pregnant uterus.
Species:  Mouse
Technique:  in situ hybridisation.
References:  109
CNS: hippocampus, dentate gyrus, hypothalamic and thalamic nuclei, cortex, caudate putamen, olfactory tubercle, nucleus accumbens
Species:  Rat
Technique:  in situ hybridisation.
References:  20
CNS: nucleus accumbens, pyramidal and molecular layers of the hippocampus, granular cell layer of the dentate gyrus, midline nuclei of the thalamus, hindbrain regions > striatum.
Species:  Rat
Technique:  Radioligand binding.
References:  92
Ear: cochlea.
Species:  Rat
Technique:  RT-PCR and immunocytochemistry.
References:  33
CNS: amygdala, olfactory tubercle, nucleus accumbens, caudate putamen, medial preoptic area, hypothalamus, median eminence, periventricular thalamus, interpeduncular nucleus.
Species:  Rat
Technique:  Radioligand binding.
References:  50
CNS: telencephalon, diencephalon > mesencephalon, metencephalon.
Species:  Rat
Technique:  Radioligand binding.
References:  63
CNS: κ receptors only represent a small percentage of opioid receptors in the superficial layers (I and II) of the dorsal horn of the spinal cord.
Species:  Rat
Technique:  Radioligand binding.
References:  7
κ1: CNS: claustrum, endopiriform nucleus, caudate putamen, nucleus accumbens, midline nuclear group of the thalamus, superficial grey layer of the superior colliculus, central grey.
κ2: CNS: caudate putamen, nucleus accumbens, amygdala, thalamus, interpeduncular nuclei.
Species:  Rat
Technique:  Radioligand binding.
References:  97
CNS: ventral forebrain, hypothalamus, thalamus, posterior pituitary, and midbrain. Primarily postsynaptic membranes.
Species:  Rat
Technique:  Immunohistochemistry.
References:  3
Tissue Distribution Comments
κ opioid receptors show a fairly widespread distribution although quantitatively they represent only a small percentage of the total opioid receptors in the brain. This contrasts with the guinea-pig brain, where κ opioid receptor expression is far more abundant. In all species, the early receptor autoradiography was carried out with low selectivity ligands such as [3H]ethylketocycazocine and [3H]bremazocine and their cross labelling of μ and δ receptors was supressed by the use of excess cold ligands to displace their binding to μ and δ opioid sites. Since the late 1980s highly selective κ opioid receptor ligands such as [3H]U69,593 and [3H]CI-977 have been used and the distribution is more restrictive when these ligands are employed.
For a review of κ opioid receptor expression in the rat see [49].

Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays
Measurement of cAMP levels in PC-12 cells transfected with the mouse κ receptor.
Species:  Mouse
Tissue:  PC-12 cells.
Response measured:  Inhibition of cAMP accumulation.
References:  90
Measurement of musculature contraction of sections of mouse vas deferens following stimulation of the intramural nerves.
Species:  Mouse
Tissue:  Vas deferens.
Response measured:  Inhibition of electrically-evoked contractions.
References:  13
Measurement of K+ conductance, using a 2 electrode voltage clamp, in Xenopus oocytes transfected with the rat κ receptor and Kir3 channel.
Species:  Rat
Tissue:  Xenopus oocytes.
Response measured:  Increase in K+ conductance.
References:  25
Measurement of Ca2+ conductance, using a whole cell voltage clamp, in PC-12 cells transfected with the mouse κ receptor.
Species:  Mouse
Tissue:  PC-12 cells.
Response measured:  Increase in K+ conductance and decrease in Ca2+ conductance.
References:  90
Measurement of cAMP levels in R1.1 murine thymoma cells endogenously expressing the κ receptor.
Species:  Mouse
Tissue:  R1.1 murine thymoma cells.
Response measured:  Inhibition of cAMP accumulation.
References:  42
Measurement of cAMP levels in CHO cells transfected with the rat κ receptor.
Species:  Rat
Tissue:  CHO cells.
Response measured:  Inhibition of cAMP accumulation.
References:  5
Measurement of cAMP levels in COS-7 cells transfected with the rat κ receptor.
Species:  Rat
Tissue:  COS-7 cells.
Response measured:  Inhibition of cAMP accumulation.
References:  12
Measurement of cAMP levels in CHO cells transfected with the human κ receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Inhibition of cAMP accumulation.
References:  108
Measurement of [35S]GTPγS binding in CHO cells transfected with the human κ receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  [35S]GTPγS binding.
References:  107
Physiological Functions
Sedative and sensorimotor effects in rats.
Species:  Rat
Tissue:  In vivo.
References:  95,98
Water diuresis, potentially by modulation of vasopressin.
Species:  Human
Tissue:  In vivo.
References:  64,68,74
Water diuresis, potentially by modulation of vasopressin.
Species:  Rat
Tissue:  In vivo.
References:  44,86,98
Water diuresis, potentially by modulation of vasopressin.
Species:  Mouse
Tissue:  In vivo.
References:  98
Neuroendocrine effects: stimulation of prolactin release, probably by modulation of the tuberoinfundibular dopamine system.
Species:  Human
Tissue:  In vivo.
References:  38,67
Neuroendocrine effects: stimulation of prolactin release, probably by modulation of the tuberoinfundibular dopamine system.
Species:  Rat
Tissue:  In vivo.
References:  17,39
Sedative and sensorimotor effects in mice.
Species:  Mouse
Tissue:  In vivo.
References:  95,98
Sedative and interoceptive effects in humans (such as psychotomimetic, dysphoric and potentially hallucinogenic).
Species:  Human
Tissue:  In vivo.
References:  75
Modulation of dopaminergic function.
Species:  Human
Tissue:  In vivo.
References:  104
Modulation of dopaminergic function. This may be related to the κ agonist effects on hedonic states (such as causing place aversion in rodents), as well as the blockade of the reinforcing, locomotor stimulant and neurobiological effects of psychostimulants such as cocaine.
Species:  Rat
Tissue:  In vivo.
References:  16,21,48,83,87
Modulation of dopaminergic function. This may be related to the κ agonist effects on hedonic states (such as causing place aversion in rodents), as well as the blockade of the reinforcing, locomotor stimulant and neurobiological effects of psychostimulants such as cocaine.
Species:  Mouse
Tissue:  In vivo.
References:  105
Immune changes have been observed in immune cells in peripheral tissues.
Species:  Mouse
Tissue:  lymphoid cells.
References:  82,91
Immune changes have been observed in immune cells in central tissues.
Species:  Human
Tissue:  Microglial cells.
References:  10,52
Enhancement of food intake.
Species:  Rat
Tissue:  In vivo.
References:  56
Blockade of pruritus.
Species:  Mouse
Tissue:  In vivo.
References:  93
Blockade of pruritus.
Species:  Rat
Tissue:  In vivo.
References:  22
Body temperature regulation:
κ receptor activation induces hypothermia, blocked by selective κ receptor antagonists. The effect is centrally mediated, involving both oxidative metabolism and heat exchange.
Species:  Rat
Tissue:  In vivo.
References:  1,24
Antinociception: systemic administration.
Species:  Rat
Tissue:  In vivo.
References:  79,98
Antinociception: systemic administration.
Species:  Mouse
Tissue:  In vivo.
References:  58,98
Antinociception: systemic administration.
Species:  Human
Tissue:  In vivo.
References:  65
Peripheral antinociception.
Species:  Rat
Tissue:  In vivo.
References:  2,88
Attenuation of contractions induced by intestinal distension in the gastrointestinal tract.
Species:  Rat
Tissue:  In vivo.
References:  81
Stimulation of relief from abdominal pain and bloating.
Species:  Human
Tissue:  In vivo.
References:  14
Physiological Consequences of Altering Gene Expression
κ receptor knockout mice exhibit increased in humoral responses to antigen challenge.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  18
κ opioid receptor knockout mice exhibit enhanced sensitivity to chemical visceral pain, abolished hypolocomotor, analgesic and aversive actions of the prototypic κ receptor agonist U50488H and attenuation of morphine withdrawl.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  85
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Oprk1tm1Jep Oprk1tm1Jep/Oprk1tm1Jep
involves: C57BL/6
MGI:97439  MP:0001462 abnormal avoidance learning behavior PMID: 19864633 
Oprk1tm1Kff Oprk1tm1Kff/Oprk1tm1Kff
involves: 129S2/SvPas * C57BL/6
MGI:97439  MP:0001392 abnormal locomotor activity PMID: 9463367 
Oprk1tm1Kff Oprk1tm1Kff/Oprk1tm1Kff
involves: 129S2/SvPas * C57BL/6
MGI:97439  MP:0001970 abnormal pain threshold PMID: 9463367 
Oprk1tm1Jep Oprk1tm1Jep/Oprk1tm1Jep
involves: 129S/SvEv * 129S6/SvEvTac * C57BL/6
MGI:97439  MP:0001982 decreased chemically-elicited antinociception PMID: 16672569 
Oprk1tm1Kff Oprk1tm1Kff/Oprk1tm1Kff
involves: 129S2/SvPas * C57BL/6
MGI:97439  MP:0000623 decreased salivation PMID: 9463367 
Oprk1tm1Jep Oprk1tm1Jep/Oprk1tm1Jep
Not Specified
MGI:97439  MP:0009778 impaired behavioral response to anesthetic PMID: 11032994 
Oprk1tm1Kff Oprk1tm1Kff/Oprk1tm1Kff
involves: 129S2/SvPas * C57BL/6
MGI:97439  MP:0009757 impaired behavioral response to morphine PMID: 9463367 
Oprk1tm1Kff Oprk1tm1Kff/Oprk1tm1Kff
involves: 129S2/SvPas * C57BL/6
MGI:97439  MP:0001934 increased litter size PMID: 9463367 
Oprk1+|Oprk1tm1Kff Oprk1tm1Kff/Oprk1+
involves: 129S2/SvPas * C57BL/6
MGI:97439  MP:0001934 increased litter size PMID: 9463367 
Biologically Significant Variant Comments
κ1 and κ2 receptor subtypes have been proposed based on in vivo pharmacology showing lack of cross-tolerance between U69,593 and bremazocine and differential antagonism by quadazocine and (-)UPHIT [27-29]. Receptor binding studies have led to suggestions of κ1, κ2 and κ3 subtypes [15,77]. However, only one κ receptor cDNA clone has been reported and no κ receptor variants have been characterised. Interaction between κ and δ receptors in transfected cells has been reported and suggested to result in κ2 subtype pharmacology [34]. Multiple active conformations of the κ receptor are likely to exist. κ receptor subtypes are likely due to interaction of receptor with other proteins or receptors at the level of neuronal circuitry, but not mRNA variants.
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To cite this database page, please use the following:

Anna Borsodi, Girolamo Caló, Charles Chavkin, MacDonald J. Christie, Olivier Civelli, Brian M. Cox, Lakshmi A. Devi, Christopher Evans, Graeme Henderson, Volker Höllt, Brigitte Kieffer, Ian Kitchen, Mary-Jeanne Kreek, Lee-Yuan Liu-Chen, Jean-Claude Meunier, Philip S. Portoghese, Toni S. Shippenberg, Eric J. Simon, Lawrence Toll, John R. Traynor, Hiroshi Ueda, Yung H. Wong.
Opioid receptors: κ receptor. Last modified on 11/06/2014. Accessed on 20/09/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=318.

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