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δ receptor

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Target not currently curated in GtoImmuPdb

Target id: 317

Nomenclature: δ receptor

Family: Opioid receptors

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 372 1p36.1-p34.3 OPRD1 opioid receptor delta 1 46,87
Mouse 7 372 4 D1-D3 Oprd1 opioid receptor, delta 1 26,44,101
Rat 7 372 5q36 Oprd1 opioid receptor, delta 1 1
Previous and Unofficial Names Click here for help
DOP | DOR | OP1 | Delta receptor | DOR-1 | DOPr | opioid receptor
Database Links Click here for help
Specialist databases
GPCRDB oprd_human (Hs), oprd_mouse (Mm), oprd_rat (Rn)
Other databases
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the delta opioid receptor bound to naltrindole
PDB Id:  4EJ4
Ligand:  naltrindole
Resolution:  3.4Å
Species:  Mouse
References:  35
Image of receptor 3D structure from RCSB PDB
Description:  1.8A resolution crystal structure of residues 36–338 of δ receptor with an N-terminal b562RIL (BRIL) fusion protein.
PDB Id:  4N6H
Ligand:  naltrindole
Resolution:  1.8Å
Species:  Human
References:  27
Natural/Endogenous Ligands Click here for help
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}
endomorphin-1 {Sp: Human}
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}
Principal endogenous agonists (Human)
β-endorphin (POMC, P01189), [Leu]enkephalin (PENK, P01210), [Met]enkephalin (PENK, P01210)

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H][D-Ala2]deltorphin I Peptide Ligand is labelled Ligand is radioactive Hs Agonist 9.4 pKd 90
pKd 9.4 (Kd 4.5x10-10 M) [90]
[3H]DPDPE Peptide Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Full agonist 8.9 pKd 2
pKd 8.9 [2]
[3H]deltorphin II Peptide Ligand is labelled Ligand is radioactive Hs Full agonist 8.7 pKd 10
pKd 8.7 [10]
UFP-512 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Agonist 10.2 pKi 94
pKi 10.2 [94]
Description: Measuring displacement of [3H]-diprenorphine in vitro
AZD7268 Small molecule or natural product Primary target of this compound Hs Agonist 9.5 pKi 65
pKi 9.5 (Ki 3x10-10 M) [65]
BW373U86 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Agonist 9.5 pKi 50
pKi 9.5 (Ki 3.2x10-10 M) [50]
DSLET Peptide Click here for species-specific activity table Hs Full agonist 9.3 pKi 92
pKi 9.3 [92]
[3H]diprenorphine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Full agonist 9.3 pKi 3,92
pKi 9.3 (Ki 5.01x10-10 M) [3,92]
diprenorphine Small molecule or natural product Click here for species-specific activity table Hs Full agonist 9.3 pKi 92
pKi 9.3 [92]
DADLE Peptide Click here for species-specific activity table Hs Full agonist 9.2 pKi 92
pKi 9.2 (Ki 6.3x10-10 M) [92]
(-)-cyclazocine Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 9.1 pKi 92
pKi 9.1 [92]
DADLE Peptide Mm Full agonist 9.1 pKi 78
pKi 9.1 [78]
ADL5859 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Agonist 9.1 pKi 50
pKi 9.1 (Ki 8.4x10-10 M) [50]
(-)-bremazocine Small molecule or natural product Click here for species-specific activity table Hs Full agonist 9.0 pKi 92
pKi 9.0 [92]
β-endorphin {Sp: Human} Peptide Click here for species-specific activity table Mm Full agonist 9.0 pKi 78
pKi 9.0 [78]
DPDPE Peptide Click here for species-specific activity table Hs Full agonist 8.8 pKi 64,92
pKi 8.8 [64,92]
deltorphin II Peptide Hs Full agonist 8.8 pKi 92
pKi 8.8 [92]
etorphine Small molecule or natural product Click here for species-specific activity table Hs Full agonist 8.8 pKi 92
pKi 8.8 (Ki 1.58x10-9 M) [92]
[D-Ala2]deltorphin II Peptide Hs Full agonist 8.8 pKi 24
pKi 8.8 [24]
BU08028 Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 8.8 pKi 43
pKi 8.8 (Ki 1.59x10-9 M) [43]
BW373U86 Small molecule or natural product Click here for species-specific activity table Rn Agonist 8.7 pKi 13
pKi 8.7 (Ki 1.8x10-9 M) [13]
[Leu]enkephalin {Sp: Human, Mouse, Rat} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 8.7 pKi 92
pKi 8.7 [92]
DSTBULET Peptide Hs Full agonist 8.6 pKi 20
pKi 8.6 (Ki 2.81x10-9 M) [20]
ADL5747 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Agonist 8.6 pKi 51
pKi 8.6 (Ki 2.7x10-9 M) [51]
ethylketocyclazocine Small molecule or natural product Click here for species-specific activity table Hs Full agonist 8.5 pKi 92
pKi 8.5 (Ki 3.16x10-9 M) [92]
deltorphin II Peptide Mm Full agonist 8.5 pKi 78
pKi 8.5 [78]
carfentanil Small molecule or natural product Click here for species-specific activity table Cp Agonist 8.5 pKi 15
pKi 8.5 (Ki 3.28x10-9 M) [15]
Description: Binding affinity-displacement of [3H]DPDPE in guinea pig whole brain
[Leu]enkephalin {Sp: Human, Mouse, Rat} Peptide Ligand is endogenous in the given species Mm Full agonist 8.4 pKi 78
pKi 8.4 [78]
dynorphin A-(1-8) {Sp: Human, Mouse, Rat} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Partial agonist 8.4 pKi 92
pKi 8.4 [92]
DSLET Peptide Mm Full agonist 8.3 pKi 78
pKi 8.3 [78]
β-endorphin {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 8.3 pKi 92
pKi 8.3 [92]
nalmefene Small molecule or natural product Approved drug Click here for species-specific activity table Hs Partial agonist 8.1 pKi 92
pKi 8.1 [92]
tramadol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 8.0 pKi 96
pKi 8.0 (Ki 9.4x10-9 M) [96]
Description: Displacement of the delta antagonist naltrindole from the delta receptor expressed in CHO cells.
dynorphin-(1-11) Peptide Click here for species-specific activity table Hs Full agonist 8.0 pKi 92
pKi 8.0 [92]
DPDPE Peptide Mm Full agonist 7.9 pKi 78
pKi 7.9 [78]
dynorphin A-(1-13) {Sp: Human, Mouse, Rat} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 7.8 pKi 92
pKi 7.8 [92]
dynorphin B {Sp: Human, Mouse, Rat} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 7.8 pKi 92
pKi 7.8 [92]
cebranopadol Small molecule or natural product Click here for species-specific activity table Hs Agonist 7.7 pKi 54
pKi 7.7 (Ki 1.8x10-8 M) [54]
Description: Radioligand binding assay
hydromorphone Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 7.4 pKi 95
pKi 7.4 (Ki 3.8x10-8 M) [95]
dynorphin A {Sp: Human, Mouse, Rat} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 7.4 pKi 92
pKi 7.4 [92]
nalorphine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Partial agonist 7.4 pKi 92
pKi 7.4 [92]
(-)-pentazocine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 7.3 pKi 92
pKi 7.3 [92]
PN6047 Small molecule or natural product Hs Biased agonist 7.3 pKi 16
pKi 7.3 [16]
SNC80 Small molecule or natural product Hs Full agonist 7.2 pKi 12,77
pKi 7.2 [12,77]
normorphine Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.1 pKi 92
pKi 7.1 [92]
AR-M1000390 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Agonist 7.0 pKi 60
pKi 7.0 (Ki 1.06x10-7 M) [60]
(-)-methadone Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.9 pKi 92
pKi 6.9 [92]
morphine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 6.9 pKi 92
pKi 6.9 [92]
fentanyl Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 6.8 pKi 92
pKi 6.8 [92]
bilorphin Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.7 pKi 19
pKi 6.7 (Ki 1.9x10-7 M) [19]
dihydromorphine Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.7 pKi 92
pKi 6.7 [92]
etonitazene Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.7 pKi 92
pKi 6.7 [92]
nalbuphine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Agonist 6.2 pKi 95
pKi 6.2 (Ki 5.8x10-7 M) [95]
endomorphin-1 {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 6.1 pKi 33
pKi 6.1 [33]
SCH221510 Small molecule or natural product Click here for species-specific activity table Hs Agonist 5.5 pKi 93
pKi 5.5 (Ki 2.854x10-6 M) [93]
Description: Radioligand binding assay
oxycodegol Small molecule or natural product Click here for species-specific activity table Hs Agonist 5.4 pKi 63
pKi 5.4 (Ki 4.15x10-6 M) [63]
Description: Competitive membrane binding assay measuring displacement [3H]DPDPE from human δ receptors expressed by CHO cells.
AR-M1000390 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Agonist 9.1 pIC50 4
pIC50 9.1 (IC50 8.9x10-10 M) [4]
TAN-67 Small molecule or natural product Mm Agonist 8.4 pIC50 30
pIC50 8.4 (IC50 3.65x10-9 M) [30]
Description: Bioassay using mouse vas deferens.
α-neoendorphin {Sp: Human, Mouse, Rat} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Mm Full agonist 8.0 pIC50 101
pIC50 8.0 [101]
[Met]enkephalin {Sp: Human, Mouse, Rat} Peptide Ligand is endogenous in the given species Immunopharmacology Ligand Mm Full agonist 7.4 pIC50 101
pIC50 7.4 [101]
ethyketazocine Small molecule or natural product Click here for species-specific activity table Mm Full agonist 6.2 pIC50 101
pIC50 6.2 [101]
pethidine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist <5.0 pIC50 75
pIC50 <5.0 (IC50 >1x10-5 M) [75]
View species-specific agonist tables
Agonist Comments
The above reported affinities are based on binding to receptors in membrane preparations with buffers optimized for agonist binding. The affinity of agonists in intact cells, or in the presence of sodium and GTP/GDP analogues is often different and multiple affinity sites have been observed [47].

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 GTPγ35S binding in cell lines expressing cloned human δ receptors. Agents giving 85% or greater stimulation than that given by DPDPE have been characterized as Full Agonists [92].

Diprenorphine is a very weak partial agonist and in some assays may behave as an antagonist.

Deltorphin II is endogenous in some species of amphibians.

Alternative sources for binding information for the same ligands in different species can be found in the following reference [70].

Although many of the agonists are considered to be highly selective for the δ opioid receptor, data using δ and μ knockout mice show that ICV administration of opioids considered δ receptor selective, such as deltorphin and DPDPE can activate μ opioid receptors to elicit analgesia [82].

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 [67]. In [67] an affinity constant was not calculated for the δ receptor, but hydrocodone was reported to inhibit [3H]naltrindole binding by 37%. Similarly, we have tagged the μ receptor as the primary target of the drug hydromorphone [95].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]naltrindole Small molecule or natural product Ligand is labelled Ligand is radioactive Ligand has a PDB structure Rn Antagonist 10.4 pKd 100
pKd 10.4 (Kd 3.7x10-11 M) [100]
naltriben Small molecule or natural product Mm Antagonist 10.9 pKi 78
pKi 10.9 [78]
naltrindole Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Mm Antagonist 10.7 pKi 78
pKi 10.7 [78]
naltriben Small molecule or natural product Click here for species-specific activity table Hs Antagonist 10.0 pKi 89,92
pKi 10.0 (Ki 1x10-10 M) [89,92]
naltriben Small molecule or natural product Rn Inverse agonist 10.0 pKi 66
pKi 10.0 [66]
UFP-505 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.8 pKi 21-22
pKi 9.8 [21-22]
naltrindole Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 9.7 pKi 74,92
pKi 9.7 [74,92]
BNTX Small molecule or natural product Mm Antagonist 9.2 pKi 78
pKi 9.2 [78]
naldemedine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 9.0 pKi 40
pKi 9.0 (Ki 9.1x10-10 M) [40]
TIPPψ Small molecule or natural product Hs Inverse agonist 9.0 pKi 84,92
pKi 9.0 [84,92]
quadazocine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.9 pKi 92
pKi 8.9 [92]
eluxadoline Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 8.9 pKi 8
pKi 8.9 (Ki 1.3x10-9 M) [8]
BNTX Small molecule or natural product Rn Inverse agonist 8.7 pKi 66
pKi 8.7 [66]
samidorphan Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.6 pKi 97
pKi 8.6 (Ki 2.6x10-9 M) [97]
BNTX Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.4 pKi 92
pKi 8.4 [92]
nor-binaltorphimine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.2 pKi 92
pKi 8.2 [92]
naltrexone Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.0 pKi 92
pKi 8.0 [92]
alvimopan Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.9 pKi 49
pKi 7.9 (Ki 1.2x10-8 M) [49]
β-FNA Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.9 pKi 92
pKi 7.9 [92]
naloxone Small molecule or natural product Approved drug Click here for species-specific activity table Mm Antagonist 7.8 pKi 78
pKi 7.8 [78]
AT-076 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.7 pKi 92,103
pKi 7.7 (Ki 1.96x10-8 M) [92,103]
Description: Radioligand binding assay
ICI 174,864 Peptide Rn Inverse agonist 7.4 pKi 66
pKi 7.4 [66]
naloxone Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 7.2 pKi 92
pKi 7.2 [92]
LY2456302 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.8 pKi 80
pKi 6.8 (Ki 1.55x10-7 M) [80]
naltrexone Small molecule or natural product Approved drug Click here for species-specific activity table Mm Antagonist 6.8 pKi 78
pKi 6.8 [78]
NFP Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.8 pKi 104
pKi 6.8 (Ki 1.57x10-7 M) [104]
Description: In a competitive radioligand membrane binding assay measuring displacement of [3H]diprenorphine by NFP from δ receptor expressed in CHO cells.
CTAP Peptide Click here for species-specific activity table Hs Antagonist 6.4 pKi 92
pKi 6.4 [92]
methylnaltrexone Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 6.1 pKi 95
pKi 6.1 (Ki 9x10-7 M) [95]
zyklophin Peptide Click here for species-specific activity table Hs Antagonist <5.0 pKi 69
pKi <5.0 (Ki >1x10-5 M) [69]
nor-binaltorphimine Small molecule or natural product Click here for species-specific activity table Mm Antagonist 6.7 pIC50 101
pIC50 6.7 [101]
naloxone Small molecule or natural product Approved drug Click here for species-specific activity table Mm Antagonist 6.2 pIC50 101
pIC50 6.2 [101]
BTRX-335140 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.2 pIC50 37
pIC50 5.2 (IC50 6.5x10-6 M) [37]
View species-specific antagonist tables
Antagonist Comments
δ opioid receptors were one of the first G protein-coupled receptors to be shown to exhibit constitutive activity [18]. As observed with agonist binding affinities, some antagonist affinities can be modulated markedly by ions and GTP/GDP analogues [66]. The assigning of an antagonist as an inverse agonist or neutral antagonist appears to be dependent upon the state of the receptor, and following agonist treatment many neutral antagonists and weak partial agonists have been reported to become inverse agonists [55].
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
BMS-986187 Small molecule or natural product Hs Positive 8.1 pKi
pKi 8.1 (Ki 7x10-9 M) BMS-986187 significantly increased the binding affinity of Leu-Enkephalin from 221 nM to 7 nM
Allosteric Modulator Comments
Although no small molecules are considered direct allosteric regulators of δ 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 number of proteins such as G protein-coupled receptor kinases, β-arrestins and G proteins clearly regulate receptor affinities and function. Furthermore, sodium and guanyl nucleotides can modify the functional δ opioid receptor complex and G protein interaction. Also, other G protein-coupled receptors appear to be able to form heterodimers with δ opioid receptors potentially modifying δ opioid activity [79] reviewed in [14,25].
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 16 [PMID: 31498617] Small molecule or natural product Click here for species-specific activity table Hs Binding 5.6 pKi 76
pKi 5.6 (Ki 2.47x10-6 M) [76]
Description: Receptor binding in a radioligand displacement assay using [3H]DADLE as tracer.
Immuno Process Associations
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes
GO:0019221 cytokine-mediated signaling pathway TAS
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
Phospholipase C stimulation
Potassium channel
Calcium channel
Other - See Comments
Comments:  δ receptors have been shown to modulate many kinase cascades including ERKs, Akts, JNKs, STAT3, P38 involving Src, Ras, Rac, Raf-1, Cdc42, RTKs.
References:  42,48,56,85
Tissue Distribution Click here for help
Immune cells.
Species:  Human
Technique:  RT-PCR.
References:  31
Skin.
Species:  Human
Technique:  RT-PCR and Immunohistochemistry.
References:  81
Detailed description of the location of δ receptors was determined in comparison with μ receptors using fluorescent knock-in technology. &delta-eGFP receptor knock-in mice were bred with μ m-Cherry receptor knock-in mice to produce a double fluorescent mouse. In the forebrain, μ and δ were mainly found in separate neurons. Considerable neuronal co-localization was detected in subcortical networks essential for survival. These networks were involved in eating and sexual behaviour, as well as perception and response to aversive stimuli.
Species:  Mouse
Technique:  Immunohistochemistry.
References:  23
Pregnant uterus and placenta.
Species:  Mouse
Technique:  in situ hybridisation.
References:  107
CNS: cortex, olfactory bulb, olfactory tubercle, caudate putamen, nucleus accumbens, amygdala.
Species:  Mouse
Technique:  Radioligand binding.
References:  34,45
Embryo:
CNS: medial habenula, hypothalamus, pons, medulla, dorsal root ganglion, caudate putamen, medial habenula, tegmentum, trigeminal nucleus.
Periphery: heart, limb bud, tooth, olfactory epithelium.
Species:  Mouse
Technique:  in situ hybridisation.
References:  105
δ receptors were localized using fluorescent knock-in technology with eGFP attached to the carboxy terminal of the δ receptor. Cellular distribution and internalization also demonstrated.
Species:  Mouse
Technique:  Immunohistochemistry.
References:  73,83
Intestine.
Species:  Mouse
Technique:  RT-PCR.
References:  72
Ear: cochlea.
Species:  Rat
Technique:  RT-PCR and immunocytochemistry.
References:  41
Widely distributed throughout the CNS, most prominant expression in the forebrain regions.
Caudate putamen, nucleus accumbens, amygdala, pontine nucleus, olfactory bulb, olfactory tubercle > interpeduncular nucleus, cortex (most dense in layers II-III and V-VI) > thalamus, hypothalamus, stria terminalis, hippocampus, globus pallidus, preoptic area, colliculi.
Virtually no binding in the periaqueductal grey and raphe nuclei.
Species:  Rat
Technique:  Radioligand binding.
References:  7,59
Autoradiographic binding with [3H]DPDPE and [3H]DSLET, in an attempt to demonstrate differential distribution of DOP subtypes, showed no major differences in receptor distribution although regional differences in binding levels between the two δ ligands were observed.
Brain: dorsomedial hypothalamus, ventromedial hypothalamus, superior colliculis, medial division of bed nucleus stria terminalis, external cortex of the inferior colliculis, amygdaloid nuclei, cingulate cortex, CA1, CA2, and CA3 regions of Ammon's horn, dentate gyrus, laminar VI of the frontal, forelimb, hindlimb and parietal cortices, nucleus accumbens, caudate/putamen.
Species:  Rat
Technique:  Radioligand binding.
References:  38
CNS: superficial layers (laminae I and II) of the dorsal horn of the spinal cord.
Species:  Rat
Technique:  Radioligand binding.
References:  5
Tissue Distribution Comments
Studies of the distribution of δ opioid receptors in humans has been limited to autoradiography and in situ hybridisation analysis [7,71]. DOP receptors in the CNS appear to have a similar distribution in rat and human [7] and mouse [34]. One notable exception is the spinal cord where DOP receptors are considerably more abundant in the dorsal horn and dorsal root ganglia than in rodent counterparts [62]. Many brain stem nuclei (such as the lateral reticular nucleus, the medial vestibular nucleus and trapezoid nucleus) express high levels of DOP mRNA yet DOP binding is undetectable [106]. For a review of δ opioid receptor expression in the rat see [58].
Expression Datasets Click here for help

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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 Click here for help
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 contraction.
References:  39
Measurement of musculature contraction of sections of mouse ileum following stimulation of the intramural nerves.
Species:  Mouse
Tissue:  Ileum.
Response measured:  Inhibition of electrically-evoked contraction.
References:  88
Measurement of cAMP levels in NG108-15 cells (a fusion of a mouse neuroblastoma, the genetic source of δ receptors, and a rat glioma cell line).
Species:  Mouse
Tissue:  NG108-15 cell line.
Response measured:  Inhibition of cAMP accumulation.
References:  86
Measurement of [35S]GTPγS binding in NG108-15 cells (a fusion of a mouse neuroblastoma, the genetic source of δ receptors, and a rat glioma cell line).
Species:  Mouse
Tissue:  NG108-15 cell line.
Response measured:  [35S]GTPγS binding.
References:  91
Physiological Functions Click here for help
Spinal analgesia in the mouse. Intrathecal injections of δ opioid agonists induce analgesia but require externalisation of δ receptors via interaction with products from the substance P precursor.
Species:  Mouse
Tissue:  Periaqueductal gray neuronal slices.
References:  36
In vivo δ receptor coupling to ion channels is not a robust phenomenon in some areas of the CNS unless the system is triggered by externalisation.
Species:  Mouse
Tissue: 
References:  36
GABAergic inhibition via δ receptors acting on locus coeruleus and hippocampal neurones has been inferred by measurement of the frequency of miniture inhibitory postsynaptic currents (IPSCs).
Species:  Rat
Tissue:  Brain slices.
References:  57,68
Reversal of thermal hyperalgesic activity by delta opioid agonists in a chronic inflammation model.
Species:  Rat
Tissue:  In vivo.
References:  11,29
Seizure promoting activity of δ receptor agonists administered systemically.
Species:  Mouse
Tissue:  In vivo.
References:  9
Studies with δ receptor knockout mice suggest the involvement of the δ receptor with spatial memory. CPP experiments suggest that the δ receptor is involved in drug spatial context association.
Species:  Mouse
Tissue:  In vivo.
References:  52-53
Physiological Functions Comments
For reviews on the signalling and function of the δ opioid receptor see [17,48,99]
Physiological Consequences of Altering Gene Expression Click here for help
Homozygote δ opioid receptor knockout mice are viable, fertile and show no gross anatomical deficits.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  28,106
δ opioid receptor knockout mice exhibit increased anxiety and depressive-like behaviour.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  28
δ opioid receptor knockout mice exhibit increased sensitivity to inflammatory pain.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  61
δ opioid receptor knockout mice exhibit modified morphine tolerance.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  106
Physiological Consequences of Altering Gene Expression Comments
Some of the physiological effects observed with knockout mice may be mouse-strain restricted and not generalise to all backgrounds.
For a review on opioid receptor knockout mice see reference [32].
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Oprd1tm1Jep Oprd1tm1Jep/Oprd1tm1Jep
involves: 129S/SvEv * C57BL/6J
MGI:97438  MP:0009748 abnormal behavioral response to addictive substance PMID: 12486185 
Oprd1tm1Jep Oprd1tm1Jep/Oprd1tm1Jep
involves: 129S/SvEv * C57BL/6J
MGI:97438  MP:0001980 abnormal chemically-elicited antinociception PMID: 12486185 
Oprd1tm1Jep|Oprm1tm1Jep Oprd1tm1Jep/Oprd1tm1Jep,Oprm1tm1Jep/Oprm1tm1Jep,Oprm1tm1Jep/Oprm1tm1Jep
involves: 129S/SvEv * 129S2/SvPas
MGI:97438  MGI:97441  MP:0008872 abnormal physiological response to xenobiotic PMID: 17544222 
Oprd1tm1Kff Oprd1tm1Kff/Oprd1tm1Kff
involves: 129/Sv * C57BL/6
MGI:97438  MP:0003064 decreased coping response PMID: 10835636 
Oprd1tm1Kff Oprd1tm1Kff/Oprd1tm1Kff
involves: 129/Sv * C57BL/6
MGI:97438  MP:0001399 hyperactivity PMID: 10835636 
Oprd1tm1Jep|Oprm1tm1Jep Oprd1tm1Jep/Oprd1tm1Jep,Oprm1tm1Jep/Oprm1tm1Jep,Oprm1tm1Jep/Oprm1tm1Jep
involves: 129S/SvEv * 129S2/SvPas
MGI:97438  MGI:97441  MP:0009778 impaired behavioral response to anesthetic PMID: 17544222 
Oprd1tm1Jep|Oprm1tm1Jep Oprd1tm1Jep/Oprd1tm1Jep,Oprm1tm1Jep/Oprm1tm1Jep,Oprm1tm1Jep/Oprm1tm1Jep
involves: 129S/SvEv * 129S2/SvPas
MGI:97438  MGI:97441  MP:0009757 impaired behavioral response to morphine PMID: 17544222 
Oprd1tm1Kff Oprd1tm1Kff/Oprd1tm1Kff
involves: 129/Sv * C57BL/6
MGI:97438  MP:0001363 increased anxiety-related response PMID: 10835636 
Oprd1tm1Dgen Oprd1tm1Dgen/Oprd1tm1Dgen
involves: 129P2/OlaHsd * C57BL/6
MGI:97438  MP:0002906 increased susceptibility to pharmacologically induced seizures
Biologically Significant Variant Comments
δ1 and δ2 receptor subtypes have been proposed based upon in vivo pharmacology of DPDPE and deltorphin II. However, no δ opioid receptor variants have been characterised as δ1 and δ2 receptor proteins, and knockout of the δ receptor gene in mice eliminates binding of the two ligands. There is mounting evidence that hetero-oligomerisation of the δ and κ opioid receptors results in the δ1 subtype and that κ/δ hetero-oligomers are functional in the spinal cord [6,28,98,102]. δ receptors have also been proposed to interact with μ receptors (for review see [102]). The observed pharmacological cross-talk may partially arise from agonist cross-reactivity. In vivo and knockout data suggest that analgesia from ICV administration of DPDPE or deltorphan II can occur via μ opioid receptors [82].

Pharmacological diversity of δ receptors likely results from interaction with different proteins (such as the formation of heterooligomers with other GPCRs) or differential posttranslational modifications as opposed to distinct variants of the primary sequence of the receptor protein [25].

References

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