κ receptor

Target id: 318

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.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for κ receptor in GtoImmuPdb

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 60,97,127
Mouse 7 380 1 A2-A3 Oprk1 opioid receptor 8,43,56,72,121
Rat 7 380 5q11 Oprk1 opioid receptor 15,54,62-63,71
Previous and Unofficial Names
KOR-1 | Kappa receptor | OP2 | KOP | KOPr
Database Links
Specialist databases
GPCRDB oprk_human (Hs), oprk_mouse (Mm), oprk_rat (Rn)
Other databases
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
SynPHARM
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:  120
Natural/Endogenous Ligands
big dynorphin {Sp: Human, Mouse, Rat}
dynorphin A-(1-13) {Sp: Human, Mouse, Rat}
dynorphin A {Sp: Human, Mouse, Rat}
dynorphin A-(1-8) {Sp: Human, Mouse, Rat}
dynorphin B {Sp: Human, Mouse, Rat}
β-endorphin {Sp: Human} , β-endorphin {Sp: Mouse} , β-endorphin {Sp: Rat}
[Leu]enkephalin {Sp: Human, Mouse, Rat}
[Met]enkephalin {Sp: Human, Mouse, Rat}
α-neoendorphin {Sp: Human, Mouse, Rat}
β-neoendorphin {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)

Download all structure-activity data for this target as a CSV file

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 118
pKd 10.1 [118]
ethyketazocine Hs Full agonist 9.4 pKd 128
pKd 9.4 [128]
enadoline Hs Full agonist 8.6 – 9.2 pKd 31
pKd 8.6 – 9.2 [31]
[3H]U69593 Hs Full agonist 8.7 – 8.8 pKd 46,77,97
pKd 8.7 – 8.8 (Kd 2x10-9 – 1.6x10-9 M) [46,77,97]
(-)-bremazocine Hs Partial agonist 10.5 pKi 110
pKi 10.5 [110]
dynorphin A {Sp: Human, Mouse, Rat} Rn Full agonist 10.0 – 10.3 pKi 54,62
pKi 10.0 – 10.3 [54,62]
ethylketocyclazocine Hs Full agonist 10.0 pKi 110
pKi 10.0 [110]
(-)-cyclazocine Hs Partial agonist 10.0 pKi 110
pKi 10.0 [110]
dynorphin A-(1-13) {Sp: Human, Mouse, Rat} Hs Full agonist 9.3 – 10.7 pKi 77,110
pKi 9.3 – 10.7 [77,110]
butorphanol Hs Partial agonist 9.9 pKi 21
pKi 9.9 (Ki 1.2x10-10 M) [21]
Description: Displacement of [3H]U69593 from human κ opioid receptor expressed in CHO cells.
dynorphin A-(1-13) {Sp: Human, Mouse, Rat} Rn Full agonist 9.9 pKi 62
pKi 9.9 [62]
dynorphin-(1-11) Hs Full agonist 9.7 pKi 110
pKi 9.7 [110]
etorphine Hs Full agonist 9.7 pKi 110
pKi 9.7 [110]
GR 89696 Hs Full agonist 9.7 pKi 83
pKi 9.7 [83]
enadoline Hs Full agonist 9.6 pKi 36,69
pKi 9.6 [36,69]
probe 1.1 [PMID: 24187130] Hs Agonist 9.6 pKi 126
pKi 9.6 (Ki 2.5x10-10 M) [126]
dynorphin A {Sp: Human, Mouse, Rat} Hs Full agonist 8.3 – 10.8 pKi 77,97,110,127-128
pKi 8.3 – 10.8 [77,97,110,127-128]
dynorphin B {Sp: Human, Mouse, Rat} Rn Full agonist 9.5 pKi 62
pKi 9.5 [62]
U69593 Hs Full agonist 9.5 pKi 46,110
pKi 9.5 [46,110]
naloxone benzoylhydrazone Hs Partial agonist 9.5 pKi 110
pKi 9.5 [110]
probe 2.1 [PMID: 24187130] Hs Agonist 9.5 pKi 126
pKi 9.5 (Ki 3.5x10-10 M) [126]
α-neoendorphin {Sp: Human, Mouse, Rat} Rn Full agonist 8.9 – 10.0 pKi 54,62
pKi 8.9 – 10.0 [54,62]
HS665 Hs Full agonist 9.3 pKi 102
pKi 9.3 (Ki 4.9x10-10 M) [102]
α-neoendorphin {Sp: Human, Mouse, Rat} Hs Full agonist 8.3 – 10.2 pKi 97,127
pKi 8.3 – 10.2 [97,127]
β-neoendorphin {Sp: Human, Mouse, Rat} Rn Full agonist 9.1 pKi 62
pKi 9.1 [62]
E2078 Hs Full agonist 9.1 pKi 84
pKi 9.1 [84]
dynorphin B {Sp: Human, Mouse, Rat} Hs Partial agonist 8.1 – 9.9 pKi 77,97,110
pKi 8.1 – 9.9 [77,97,110]
spiradoline Rn Full agonist 9.0 pKi 15
pKi 9.0 [15]
asimadoline Cp Agonist 9.0 pKi 27
pKi 9.0 (Ki 1x10-9 M) [27]
Description: Displacement of [3H]- 69593 from K opioid receptors from guinea pig cerebellum.
dynorphin A-(1-8) {Sp: Human, Mouse, Rat} Hs Full agonist 8.0 – 9.9 pKi 77,97,110,122
pKi 8.0 – 9.9 [77,97,110,122]
ethyketazocine Rn Full agonist 8.8 pKi 62
pKi 8.8 [62]
E2078 Rn Full agonist 8.8 pKi 62
pKi 8.8 [62]
ICI 204448 Rn Full agonist 8.8 pKi 15
pKi 8.8 [15]
tifluadom Hs Full agonist 8.8 pKi 128
pKi 8.8 [128]
U50488 Hs Agonist 7.8 – 9.7 pKi 14,77,97,110,117,127-128
pKi 7.8 – 9.7 [14,77,97,110,117,127-128]
cebranopadol Hs Agonist 8.6 pKi 55
pKi 8.6 (Ki 2.6x10-9 M) [55]
Description: Radioligand binding assay
hydromorphone Hs Agonist 8.6 pKi 119
pKi 8.6 (Ki 2.8x10-9 M) [119]
nalorphine Hs Partial agonist 7.9 – 9.1 pKi 110,128
pKi 7.9 – 9.1 [110,128]
U50488 Rn Partial agonist 8.2 – 8.7 pKi 15,54,62
pKi 8.2 – 8.7 [15,54,62]
U69593 Rn Full agonist 8.0 – 8.7 pKi 15,62
pKi 8.0 – 8.7 [15,62]
salvinorin A Hs Full agonist 7.8 – 8.7 pKi 11,88
pKi 7.8 – 8.7 [11,88]
BU08028 Hs Agonist 8.3 pKi 40
pKi 8.3 (Ki 5.63x10-9 M) [40]
compound 3 [PMID: 23134120] Hs Partial agonist 8.2 pKi 102
pKi 8.2 (Ki 5.9x10-9 M) [102]
(-)-pentazocine Hs Partial agonist 7.8 – 8.6 pKi 110,128
pKi 7.8 – 8.6 [110,128]
β-neoendorphin {Sp: Human, Mouse, Rat} Hs Full agonist 7.9 pKi 97
pKi 7.9 [97]
tramadol Hs Agonist 7.8 pKi 119
pKi 7.8 (Ki 1.4x10-8 M) [119]
Description: Displacement of the kappa agonist U69593 from the kappa receptor expressed in CHO cells.
normorphine Hs Full agonist 7.8 pKi 110
pKi 7.8 [110]
ADL5747 Hs Agonist 7.6 pKi 51
pKi 7.6 (Ki 2.5x10-8 M) [51]
BW373U86 Rn Agonist 7.5 pKi 12
pKi 7.5 (Ki 3.4x10-8 M) [12]
nalbuphine Hs Full agonist 7.4 – 7.5 pKi 128
pKi 7.4 – 7.5 [128]
ADL5859 Hs Agonist 7.4 pKi 50
pKi 7.4 (Ki 3.7x10-8 M) [50]
morphine Hs Partial agonist 7.3 pKi 110
pKi 7.3 [110]
cebranopadol Rn Agonist 7.2 pKi 55
pKi 7.2 (Ki 6.4x10-8 M) [55]
Description: Radioligand binding assay
β-endorphin {Sp: Human} Hs Partial agonist 6.3 – 7.9 pKi 97,110
pKi 6.3 – 7.9 [97,110]
dihydromorphine Hs Partial agonist 7.1 pKi 110
pKi 7.1 [110]
fentanyl Hs Partial agonist 7.1 pKi 110
pKi 7.1 [110]
etonitazene Hs Partial agonist 6.9 pKi 110
pKi 6.9 [110]
BW373U86 Hs Agonist 6.9 pKi 50
pKi 6.9 (Ki 1.3x10-7 M) [50]
SCH221510 Hs Agonist 6.9 pKi 115
pKi 6.9 (Ki 1.31x10-7 M) [115]
Description: Radioligand binding assay
morphine Rn Partial agonist 6.7 – 7.0 pKi 15,62
pKi 6.7 – 7.0 [15,62]
β-endorphin {Sp: Human} Rn Full agonist 6.8 pKi 62
pKi 6.8 [62]
UFP-512 Hs Agonist 6.7 pKi 116
pKi 6.7 [116]
Description: Measuring displacement of [3H]-diprenorphine in vitro
hydrocodone Hs Agonist 6.6 pKi 70
pKi 6.6 (Ki 2.6x10-7 M) [70]
(-)-methadone Hs Partial agonist 6.5 pKi 110
pKi 6.5 [110]
DAMGO Hs Partial agonist 6.5 pKi 110
pKi 6.5 [110]
SR16835 Hs Agonist 6.2 pKi 111
pKi 6.2 (Ki 6.813x10-7 M) [111]
Description: Radioligand binding assay
[Leu]enkephalin {Sp: Human, Mouse, Rat} Rn Full agonist 6.0 pKi 62
pKi 6.0 [62]
[Met]enkephalin {Sp: Human, Mouse, Rat} Rn Full agonist 6.0 pKi 62
pKi 6.0 [62]
DAMGO Rn Partial agonist 5.9 pKi 62
pKi 5.9 [62]
difelikefalin Mm Agonist 10.3 pEC50 93
pEC50 10.3 (EC50 4.8x10-11 M) [93]
difelikefalin Hs Agonist 9.8 pEC50 93
pEC50 9.8 (EC50 1.6x10-10 M) [93]
HS665 Hs Full agonist 8.4 pEC50 102
pEC50 8.4 (EC50 3.62x10-9 M) [102]
Description: Measuring stimulation of [35S]GTPγS binding.
compound 3 [PMID: 23134120] Hs Partial agonist 7.5 pEC50 102
pEC50 7.5 (EC50 3.5x10-8 M) [102]
Description: Measuring stimulation of [35S]GTPγS binding.
probe 1.1 [PMID: 24187130] Hs Biased agonist 5.4 – 7.5 pEC50 126
pEC50 7.5 (EC50 3.1x10-8 M) [126]
Description: Measuring [35S]GTPγS binding
pEC50 5.4 (EC50 4.129x10-6 M) [126]
Description: Measuring βarrestin2 recruitment
probe 2.1 [PMID: 24187130] Hs Biased agonist 5.0 – 7.1 pEC50 126
pEC50 7.1 (EC50 8.47x10-8 M) [126]
Description: Measuring [35S]GTPγS binding
pEC50 <5.0 (EC50 >1x10-5 M) [126]
Description: Measuring βarrestin2 recruitment
α-neoendorphin {Sp: Human, Mouse, Rat} Mm Full agonist 10.0 pIC50 121
pIC50 10.0 [121]
dynorphin B {Sp: Human, Mouse, Rat} Mm Full agonist 10.0 pIC50 121
pIC50 10.0 [121]
dynorphin A-(1-8) {Sp: Human, Mouse, Rat} Mm Full agonist 9.7 pIC50 121
pIC50 9.7 [121]
[D-Ala2,F5,Phe4]dynorphin-(1-17)-NH2 Mm Full agonist 9.7 pIC50 121
pIC50 9.7 [121]
dynorphin-(1-17)-NH2 Mm Full agonist 9.7 pIC50 121
pIC50 9.7 [121]
(-)-bremazocine Mm Full agonist 9.5 pIC50 121
pIC50 9.5 [121]
dynorphin A {Sp: Human, Mouse, Rat} Mm Full agonist 9.4 pIC50 121
pIC50 9.4 [121]
[Met5]dynorphin-(1-17) Mm Full agonist 9.2 pIC50 121
pIC50 9.2 [121]
ethyketazocine Mm Full agonist 9.0 pIC50 121
pIC50 9.0 [121]
U50488 Mm Partial agonist 9.0 pIC50 121
pIC50 9.0 [121]
spiradoline Mm Full agonist 9.0 pIC50 121
pIC50 9.0 [121]
U69593 Mm Full agonist 8.6 pIC50 121
pIC50 8.6 [121]
ICI 204448 Mm Full agonist 8.2 pIC50 121
pIC50 8.2 [121]
[D-Ala2,F5,Phe4]dynorphin-(1-13)-NH2 Mm Full agonist 7.7 pIC50 121
pIC50 7.7 [121]
β-endorphin {Sp: Human} Mm Partial agonist 7.4 pIC50 121
pIC50 7.4 [121]
nalbuphine Mm Full agonist 7.4 pIC50 121
pIC50 7.4 [121]
pethidine Hs Agonist 5.6 pIC50 82
pIC50 5.6 (IC50 2.37x10-6 M) [82]
AR-M1000390 Hs Agonist 5.1 pIC50 4
pIC50 5.1 (IC50 7.47x10-6 M) [4]
[3H]enadoline Hs Full agonist - - 98
[98]
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 [110].

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 [70]. Similarly, we have tagged the μ receptor as the primary target of the drug hydromorphone [119].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
LY2456302 Hs Antagonist 9.1 pKB 87
pKB 9.1 (KB 8.13x10-10 M) [87]
Description: Measuring inhibition of agonist-induced [35S]GTPγS binding in vitro.
zyklophin Hs Antagonist 7.1 pKB 76
pKB 7.1 (KB 8.39x10-8 M) [76]
Description: Schild analysis of zyklophin vs. Dynorphin A-(1-13)NH2
[3H]diprenorphine Hs Antagonist 9.1 pKd 3,97
pKd 9.1 (Kd 7.94x10-10 M) [3,97]
nor-binaltorphimine Rn Antagonist 9.6 – 10.7 pKi 15,54,62
pKi 9.6 – 10.7 [15,54,62]
JDTic Hs Antagonist 9.0 – 11.2 pKi 66,108,124
pKi 11.2 (Ki 6x10-12 M) [108]
Description: Measuring antagonism of U50,488-induced [35S]GTPγS binding
pKi 9.0 – 9.4 (Ki 1x10-9 – 3.98x10-10 M) [66,108,124]
nor-binaltorphimine Hs Antagonist 8.9 – 11.0 pKi 77,81,97,110,127-128
pKi 8.9 – 11.0 [77,81,97,110,127-128]
5'-guanidinonaltrindole Hs Antagonist 9.7 – 9.9 pKi 37,77,104
pKi 9.7 – 9.9 [37,77,104]
β-FNA Hs Antagonist 9.7 pKi 110
pKi 9.7 [110]
quadazocine Hs Antagonist 9.7 pKi 110
pKi 9.7 [110]
diprenorphine Hs Antagonist 9.6 – 9.7 pKi 77,110,127-128
pKi 9.6 – 9.7 [77,110,127-128]
buprenorphine Hs Antagonist 9.1 – 10.2 pKi 110,128
pKi 9.1 – 10.2 [110,128]
nalmefene Hs Antagonist 9.5 pKi 110
pKi 9.5 [110]
LY2456302 Hs Antagonist 9.1 pKi 87
pKi 9.1 (Ki 8.07x10-10 M) [87]
AT-076 Hs Antagonist 8.9 pKi 110,124
pKi 8.9 (Ki 1.14x10-9 M) [110,124]
Description: Radioligand binding assay
naltrexone Hs Antagonist 8.4 – 9.4 pKi 77,97,110
pKi 8.4 – 9.4 [77,97,110]
BNTX Hs Antagonist 8.4 pKi 110
pKi 8.4 [110]
naltriben Hs Antagonist 8.4 pKi 110
pKi 8.4 [110]
methylnaltrexone Hs Antagonist 8.2 pKi 119
pKi 8.2 (Ki 6.3x10-9 M) [119]
naloxone Hs Antagonist 7.6 – 8.6 pKi 77,97,110,127-128
pKi 7.6 – 8.6 [77,97,110,127-128]
naltrindole Hs Antagonist 8.0 pKi 110
pKi 8.0 [110]
naltrindole Rn Antagonist 7.9 pKi 54
pKi 7.9 [54]
naloxone Rn Antagonist 7.7 – 8.0 pKi 15,54,62
pKi 7.7 – 8.0 [15,54,62]
zyklophin Hs Antagonist 7.5 pKi 76
pKi 7.5 (Ki 3.03x10-8 M) [76]
alvimopan Hs Antagonist 7.0 pKi 49
pKi 7.0 (Ki 1x10-7 M) [49]
(+)-naloxone Rn Antagonist 4.7 pKi 62
pKi 4.7 [62]
naltrexone Mm Antagonist 9.2 pIC50 121
pIC50 9.2 [121]
nor-binaltorphimine Mm Antagonist 8.9 pIC50 121
pIC50 8.9 [121]
naloxone Mm Antagonist 8.3 pIC50 121
pIC50 8.3 [121]
naltrindole Mm Antagonist 7.4 pIC50 121
pIC50 7.4 [121]
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:  6,28,30,42,48,64,92,105
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 [10].
κ opioid receptors interact with NHERF-1/EBP50 to stimulate Na+/H+ exchange independent of Gi/o proteins [35].
References:  10,35,47,53,67,113
Tissue Distribution
Immune cells.
Species:  Human
Technique:  RT-PCR.
References:  23
CNS: amygdala, caudate nucleus, hypothalamus, subthalamic nucleus > hippocampus, thalamus > substantia nigra, corpus callosum.
Species:  Human
Technique:  Northern blotting.
References:  127
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:  97
Skin.
Species:  Human
Technique:  RT-PCR and Immunohistochemistry.
References:  90
Pregnant uterus.
Species:  Mouse
Technique:  in situ hybridisation.
References:  130
CNS: claustrum, nucleus accumbens, endopiriform nucleus, ventral pallidum, preoptic area, fundus striati, hypothalamus, substantia nigra.
Species:  Mouse
Technique:  Radioligand binding.
References:  41
CNS: olfactory tubercle, endopiriform nucleus, ventral pallidum, hypothalamus, deep cortical layers, claustrum.
Species:  Mouse
Technique: