Nomenclature: δ 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 7 372 1p36.1-p34.3 OPRD1 opioid receptor, delta 1 30,58
Mouse 7 372 4 D1-D3 Oprd1 opioid receptor, delta 1 14,28,67
Rat 7 372 5q36 Oprd1 opioid receptor, delta 1 1
Previous and Unofficial Names
DOR-1
delta
DOR
OP1
DOP
Delta opioid receptor
D-OR-1
Opioid receptor delta 1
delta-type opioid receptor
opioid receptor A
opioid receptor, delta 1
Nbor
mDOR
DOP-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 delta opioid receptor bound to naltrindole
PDB Id:  4EJ4
Ligand:  naltrindole
Resolution:  3.4Å
Species:  Mouse
References:  22
Natural/Endogenous Ligands
β-endorphin {Sp: Human} , β-endorphin {Sp: Rat} , β-endorphin {Sp: Mouse}
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}
endomorphin-1 {Sp: Human}
[Leu]enkephalin {Sp: Human, Mouse, Rat}
[Met]enkephalin {Sp: Human, Mouse, Rat}
Principal endogenous agonists (Human)
β-endorphin (POMC, P01189), [Leu]enkephalin (PENK, P01210), [Met]enkephalin (PENK, P01210)
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[D-Ala2]deltorphin I Hs Agonist 9.35 pKd 12,61
pKd 9.35 (Kd 4.5x10-10 M) [12,61]
[3H]diprenorphine Hs Full agonist 9.3 pKi 63
pKi 9.3 [63]
DSLET Hs Full agonist 9.3 pKi 63
pKi 9.3 [63]
diprenorphine Hs Full agonist 9.3 pKi 63
pKi 9.3 [63]
DADLE Hs Full agonist 9.2 pKi 63
pKi 9.2 [63]
(-)-cyclazocine Hs Partial agonist 9.1 pKi 63
pKi 9.1 [63]
DADLE Mm Full agonist 9.1 pKi 51
pKi 9.1 [51]
β-endorphin {Sp: Human} Mm Full agonist 9.0 pKi 51
pKi 9.0 [51]
(-)-bremazocine Hs Full agonist 9.0 pKi 63
pKi 9.0 [63]
deltorphin II Hs Full agonist 8.8 pKi 63
pKi 8.8 [63]
DPDPE Hs Full agonist 8.8 pKi 41,63
pKi 8.8 [41,63]
etorphine Hs Full agonist 8.8 pKi 63
pKi 8.8 [63]
[D-Ala2]deltorphin II Hs Full agonist 8.8 pKi 13
pKi 8.8 [13]
[Leu]enkephalin {Sp: Human, Mouse, Rat} Hs Full agonist 8.7 pKi 63
pKi 8.7 [63]
DSTBULET Hs Full agonist 8.6 pKi 11
pKi 8.6 (Ki 2.81x10-9 M) [11]
deltorphin II Mm Full agonist 8.5 pKi 51
pKi 8.5 [51]
(-)-EKC Hs Full agonist 8.5 pKi 63
pKi 8.5 [63]
dynorphin A-(1-8) {Sp: Human, Mouse, Rat} Hs Partial agonist 8.4 pKi 63
pKi 8.4 [63]
[Leu]enkephalin {Sp: Human, Mouse, Rat} Mm Full agonist 8.4 pKi 51
pKi 8.4 [51]
β-endorphin {Sp: Human} Hs Full agonist 8.3 pKi 63
pKi 8.3 [63]
DSLET Mm Full agonist 8.3 pKi 51
pKi 8.3 [51]
nalmefene Hs Partial agonist 8.1 pKi 63
pKi 8.1 [63]
dynorphin-(1-11) Hs Full agonist 8.0 pKi 63
pKi 8.0 [63]
DPDPE Mm Full agonist 7.9 pKi 51
pKi 7.9 [51]
dynorphin B {Sp: Human, Mouse, Rat} Hs Full agonist 7.8 pKi 63
pKi 7.8 [63]
dynorphin A-(1-13) {Sp: Human, Mouse, Rat} Hs Full agonist 7.8 pKi 63
pKi 7.8 [63]
hydromorphone Hs Agonist 7.42 pKi 64
pKi 7.42 (Ki 3.8x10-8 M) [64]
nalorphine Hs Partial agonist 7.4 pKi 63
pKi 7.4 [63]
dynorphin A {Sp: Human, Mouse, Rat} Hs Full agonist 7.4 pKi 63
pKi 7.4 [63]
(-)-pentazocine Hs Full agonist 7.3 pKi 63
pKi 7.3 [63]
SNC80 Hs Full agonist 7.2 pKi 7,50
pKi 7.2 [7,50]
normorphine Hs Full agonist 7.1 pKi 63
pKi 7.1 [63]
morphine Hs Full agonist 6.9 pKi 63
pKi 6.9 [63]
(-)-methadone Hs Full agonist 6.9 pKi 63
pKi 6.9 [63]
fentanyl Hs Full agonist 6.8 pKi 63
pKi 6.8 [63]
etonitazene Hs Full agonist 6.7 pKi 63
pKi 6.7 [63]
dihydromorphine Hs Full agonist 6.7 pKi 63
pKi 6.7 [63]
nalbuphine Hs Agonist 6.24 pKi 64
pKi 6.24 (Ki 5.8x10-7 M) [64]
endomorphin-1 {Sp: Human} Hs Full agonist 6.1 pKi 20
pKi 6.1 [20]
α-neoendorphin {Sp: Human, Mouse, Rat} Mm Full agonist 8.0 pIC50 67
pIC50 8.0 [67]
[Met]enkephalin {Sp: Human, Mouse, Rat} Mm Full agonist 7.4 pIC50 67
pIC50 7.4 [67]
EKC Mm Full agonist 6.2 pIC50 67
pIC50 6.2 [67]
meperidine Hs Agonist <5.0 pIC50 49
pIC50 <5.0 (IC50 >1x10-5 M) [49]
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 [31].

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 [63].

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 [45].

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 [54].

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 [43]. In [43] 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[64].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
naltriben Mm Antagonist 10.9 pKi 51
pKi 10.9 [51]
naltrindole Mm Antagonist 10.7 pKi 51
pKi 10.7 [51]
naltriben Rn Inverse agonist 10.0 pKi 42
pKi 10.0 [42]
naltriben Hs Antagonist 10.0 pKi 60,63
pKi 10.0 [60,63]
naltrindole Hs Antagonist 9.7 pKi 48,63
pKi 9.7 [48,63]
BNTX Mm Antagonist 9.2 pKi 51
pKi 9.2 [51]
TIPPψ Hs Inverse agonist 9.0 pKi 55,63
pKi 9.0 [55,63]
quadazocine Hs Antagonist 8.9 pKi 63
pKi 8.9 [63]
BNTX Rn Inverse agonist 8.7 pKi 42
pKi 8.7 [42]
BNTX Hs Antagonist 8.4 pKi 63
pKi 8.4 [63]
nor-binaltorphimine Hs Antagonist 8.2 pKi 63
pKi 8.2 [63]
naltrexone Hs Antagonist 8.0 pKi 63
pKi 8.0 [63]
alvimopan Hs Antagonist 7.92 pKi 33
pKi 7.92 (Ki 1.2x10-8 M) [33]
β-FNA Hs Antagonist 7.9 pKi 63
pKi 7.9 [63]
naloxone Mm Antagonist 7.8 pKi 51
pKi 7.8 [51]
ICI 174,864 Rn Inverse agonist 7.4 pKi 42
pKi 7.4 [42]
naloxone Hs Antagonist 7.2 pKi 63
pKi 7.2 [63]
naltrexone Mm Antagonist 6.8 pKi 51
pKi 6.8 [51]
CTAP Hs Antagonist 6.4 pKi 63
pKi 6.4 [63]
nor-binaltorphimine Mm Antagonist 6.7 pIC50 67
pIC50 6.7 [67]
naloxone Mm Antagonist 6.2 pIC50 67
pIC50 6.2 [67]
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 [10]. As observed with agonist binding affinities, some antagonist affinities can be modulated markedly by ions and GTP/GDP analogues [42]. 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 [34].
Allosteric Modulator Comments
Although no small molecules are considered direct allosteric regulators of the δ opioid receptor, 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 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 [52] reviewed in [8,15].
Primary Transduction Mechanisms
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:  27,32,35,56
Tissue Distribution
Immune cells.
Species:  Human
Technique:  RT-PCR.
References:  19
Skin.
Species:  Human
Technique:  RT-PCR and Immunohistochemistry.
References:  53
CNS: cortex, olfactory bulb, olfactory tubercle, caudate putamen, nucleus accumbens, amygdala.
Species:  Mouse
Technique:  Radioligand binding.
References:  21,29
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:  69
Intestine.
Species:  Mouse
Technique:  RT-PCR.
References:  47
Pregnant uterus and placenta.
Species:  Mouse
Technique:  in situ hybridisation.
References:  71
CNS: superficial layers (laminae I and II) of the dorsal horn of the spinal cord.
Species:  Rat
Technique:  Radioligand binding.
References:  2
Ear: cochlea.
Species:  Rat
Technique:  RT-PCR and immunocytochemistry.
References:  26
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:  24
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:  4,38
Tissue Distribution Comments
Studies of the distribution of δ opioid receptors in humans has been limited to autoradiography and in situ hybridisation analysis [4,46].
DOP receptors in the CNS appear to have a similar distribution in rat and human [4] and mouse [21]. 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 [40].
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 [70].
For a review of δ opioid receptor expression in the rat see [37].

Expression Datasets

Show »

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]

There should be a chart of expression data here, you may need to enable JavaScript!
Functional Assays
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:  25
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:  59
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:  57
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:  62
Physiological Functions
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:  23
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:  23
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:  36,44
Reversal of thermal hyperalgesic activity by delta opioid agonists in a chronic inflammation model.
Species:  Rat
Tissue:  In vivo.
References:  6,17
Seizure promoting activity of δ receptor agonists administered systemically.
Species:  Mouse
Tissue:  In vivo.
References:  5
Physiological Functions Comments
For reviews on the signalling and function of the δ opioid receptor see [9,32,66]
Physiological Consequences of Altering Gene Expression
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:  16,70
δ opioid receptor knockout mice exhibit increased anxiety and depressive-like behaviour.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  16
δ opioid receptor knockout mice exhibit increased sensitivity to inflammatory pain.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  39
δ opioid receptor knockout mice exhibit modified morphine tolerance.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  70
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 [18].
Phenotypes, Alleles and Disease Models Mouse data from MGI

Show »

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 [3,16,65,68].
δ receptors have also been proposed to interact with μ receptors (for review see [68]). 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 [54].
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 [15].

Available Assays
DiscoveRx PathHunter® CHO-K1 OPRD1 β-Arrestin Cell Line (Cat no. 93-0400C2)
PathHunter® eXpress OPRD1 CHO-K1 β-Arrestin GPCR Assay (Cat no. 93-0400E2CP2M)
PathHunter® U2OS OPRD1 β-Arrestin Cell Line (Cat no. 93-0400C3)
more info

REFERENCES

1. Abood ME, Noel MA, Farnsworth JS, Tao Q. (1994) Molecular cloning and expression of a delta-opioid receptor from rat brain. J Neurosci Res37: 714-719. [PMID:7519274]

2. Besse D, Lombard MC, Besson JM. (1991) Autoradiographic distribution of mu, delta and kappa opioid binding sites in the superficial dorsal horn, over the rostrocaudal axis of the rat spinal cord. Brain Res548: 287-291. [PMID:1651143]

3. Bhushan RG, Sharma SK, Xie Z, Daniels DJ, Portoghese PS. (2004) A bivalent ligand (KDN-21) reveals spinal delta and kappa opioid receptors are organized as heterodimers that give rise to delta(1) and kappa(2) phenotypes. Selective targeting of delta-kappa heterodimers. J Med Chem47: 2969-2972. [PMID:15163177]

4. Blackburn TP, Cross AJ, Hille C, Slater P. (1988) Autoradiographic localization of delta opiate receptors in rat and human brain. Neuroscience27: 497-506. [PMID:2851117]

5. Broom DC, Guo L, Coop A, Husbands SM, Lewis JW, Woods JH, Traynor JR. (2000) BU48: a novel buprenorphine analog that exhibits delta-opioid-mediated convulsions but not delta-opioid-mediated antinociception in mice. J Pharmacol Exp Ther294: 1195-1200. [PMID:10945877]

6. Cahill CM, Morinville A, Hoffert C, O'Donnell D, Beaudet A. (2003) Up-regulation and trafficking of delta opioid receptor in a model of chronic inflammation: implications for pain control. Pain101: 199-208. [PMID:12507715]

7. Calderon SN, Rothman RB, Porreca F, Flippen-Anderson JL, McNutt RW, Xu H, Smith LE, Bilsky EJ, Davis P, Rice KC. (1994) Probes for narcotic receptor mediated phenomena. 19. Synthesis of (+)-4-[(alpha R)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3- methoxybenzyl]-N,N-diethylbenzamide (SNC 80): a highly selective, nonpeptide delta opioid receptor agonist. J. Med. Chem.37 (14): 2125-8. [PMID:8035418]

8. Christopoulos A, Kenakin T. (2002) G protein-coupled receptor allosterism and complexing. Pharmacol Rev54: 323-374. [PMID:12037145]

9. Connor M, Christie MD. (1999) Opioid receptor signalling mechanisms. Clin Exp Pharmacol Physiol26: 493-499. [PMID:10405772]

10. Costa T, Herz A. (1989) Antagonists with negative intrinsic activity at delta opioid receptors coupled to GTP-binding proteins. Proc Natl Acad Sci U S A86: 7321-7325. [PMID:2552439]

11. Delay-Goyet P, Seguin C, Gacel G, Roques BP. (1988) [3H][D-Ser2(O-tert-butyl),Leu5]enkephalyl-Thr6 and [D-Ser2(O-tert-butyl),Leu5]enkephalyl-Thr6(O-tert-butyl). Two new enkephalin analogs with both a good selectivity and a high affinity toward delta-opioid binding sites. J. Biol. Chem.263 (9): 4124-30. [PMID:2831220]

12. Erspamer V. (1988) Discovery, isolation, and characterization of bombesin-like peptides. Ann N Y Acad Sci547: 3-9. [PMID:3071223]

13. Erspamer V, Melchiorri P, Falconieri-Erspamer G, Negri L, Corsi R, Severini C, Barra D, Simmaco M, Kreil G. (1989) Deltorphins: a family of naturally occurring peptides with high affinity and selectivity for delta opioid binding sites. Proc. Natl. Acad. Sci. U.S.A.86 (13): 5188-92. [PMID:2544892]

14. Evans C, Keith D, Morrison H, Magendzo K, Edwards R. (1992) Cloning of delta opioid receptor by functional expression. Science258: 1952-1955. [PMID:1335167]

15. Evans CJ. (2004) Secrets of the opium poppy revealed. Neuropharmacology47 Suppl 1: 293-299. [PMID:15464145]

16. Filliol D, Ghozland S, Chluba J, Martin M, Matthes HW, Simonin F, Befort K, Gaveriaux-Ruff C, Dierich A, LeMeur M, Valverde O, Maldonado R, Kieffer BL. (2000) Mice deficient for delta- and mu-opioid receptors exhibit opposing alterations of emotional responses. Nat Genet25: 195-200. [PMID:10835636]

17. Fraser GL, Gaudreau GA, Clarke PB, Ménard DP, Perkins MN. (2000) Antihyperalgesic effects of delta opioid agonists in a rat model of chronic inflammation. Br J Pharmacol129: 1668-1672. [PMID:10780972]

18. Gaveriaux-Ruff C, Kieffer BL. (2002) Opioid receptor genes inactivated in mice: the highlights. Neuropeptides36: 62-71. [PMID:12359497]

19. Gavériaux C, Peluso J, Simonin F, Laforet J, Kieffer B. (1995) Identification of kappa- and delta-opioid receptor transcripts in immune cells. FEBS Lett369: 272-276. [PMID:7649271]

20. Gong J, Strong JA, Zhang S, Yue X, Dehaven RN, Daubert JD, Cassel JA, Yu G, Mansson E, Yu L. (1998) Endomorphins fully activate a cloned human mu opioid receptor. FEBS Lett439: 152-156. [PMID:9849897]

21. Goody RJ, Oakley SM, Filliol D, Kieffer BL, Kitchen I. (2002) Quantitative autoradiographic mapping of opioid receptors in the brain of delta-opioid receptor gene knockout mice. Brain Res945: 9-19. [PMID:12113946]

22. Granier S, Manglik A, Kruse AC, Kobilka TS, Thian FS, Weis WI, Kobilka BK. (2012) Structure of the δ-opioid receptor bound to naltrindole. Nature485 (7398): 400-4. [PMID:22596164]

23. Guan JS, Xu ZZ, Gao H, He SQ, Ma GQ, Sun T, Wang LH, Zhang ZN, Lena I, Kitchen I, Elde R, Zimmer A, He C, Pei G, Bao L, Zhang X. (2005) Interaction with vesicle luminal protachykinin regulates surface expression of delta-opioid receptors and opioid analgesia. Cell122: 619-631. [PMID:16122428]

24. Hiller JM, Fan LQ, Simon EJ. (1996) Autoradiographic comparison of [3H]DPDPE and [3H]DSLET binding: evidence for distinct delta 1 and delta 2 opioid receptor populations in rat brain. Brain Res719: 85-95. [PMID:8782867]

25. Hughes J, Kosterlitz HW, Leslie FM. (1975) Effect of morphine on adrenergic transmission in the mouse vas deferens. Assessment of agonist and antagonist potencies of narcotic analgesics. Br. J. Pharmacol.53: 371-381. [PMID:236796]

26. Jongkamonwiwat N, Phansuwan-Pujito P, Sarapoke P, Chetsawang B, Casalotti SO, Forge A, Dodson H, Govitrapong P. (2003) The presence of opioid receptors in rat inner ear. Hear Res181: 85-93. [PMID:12855366]

27. Kam AY, Chan AS, Wong YH. (2003) Rac and Cdc42-dependent regulation of c-Jun N-terminal kinases by the delta-opioid receptor. J Neurochem84: 503-513. [PMID:12558970]

28. Kieffer BL, Befort K, Gaveriaux-Ruff C, Hirth CG. (1992) Delta-opioid receptor: isolation of a cDNA by expression cloning and pharmacological characerization. Proc. Natl. Acad. Sci. U.S.A.89: 12048-12052. [PMID:1334555]

29. Kitchen I, Slowe SJ, Matthes HWD, Kieffer B. (1997) Quantitative autoradiographic mapping of mu, delta and kappa-opioid receptors in knockout mice lacking the mu-opioid receptor gene. Brain Res.778: 73-88. [PMID:9462879]

30. Knapp RJ, Malatynska E, Fang L, Li X, Babin E, Nguyen M, Santoro G, Varga EV, Hruby VJ, Roeske WR. (1994) Identification of a human delta opioid receptor: cloning and expression. Life Sci54: PL463-PL469. [PMID:8201839]

31. Law PY, Hom DS, Loh HH. (1985) Multiple affinity states of opiate receptor in neuroblastoma x glioma NG108-15 hybrid cells. Opiate agonist association rate is a function of receptor occupancy. J Biol Chem260: 3561-3569. [PMID:2982865]

32. Law PY, Wong YH, Loh HH. (2000) Molecular mechanisms and regulation of opioid receptor signaling. Annu Rev Pharmacol Toxicol40: 389-430. [PMID:10836142]

33. Le Bourdonnec B, Barker WM, Belanger S, Wiant DD, Conway-James NC, Cassel JA, O'Neill TJ, Little PJ, DeHaven RN, DeHaven-Hudkins DL et al.. (2008) Novel trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines as mu opioid receptor antagonists with improved opioid receptor selectivity profiles. Bioorg. Med. Chem. Lett.18 (6): 2006-12. [PMID:18313920]

34. Liu JG, Prather PL. (2002) Chronic agonist treatment converts antagonists into inverse agonists at delta-opioid receptors. J Pharmacol Exp Ther302: 1070-1079. [PMID:12183665]

35. Lo RK, Wong YH. (2004) Signal transducer and activator of transcription 3 activation by the delta-opioid receptor via Galpha14 involves multiple intermediates. Mol Pharmacol65: 1427-1439. [PMID:15155836]

36. Lupica CR. (1995) Delta and mu enkephalins inhibit spontaneous GABA-mediated IPSCs via a cyclic AMP-independent mechanism in the rat hippocampus. J Neurosci15: 737-749. [PMID:7823176]

37. Mansour A, Fox CA, Akil H, Watson SJ. (1995) Opioid-receptor mRNA expression in the rat CNS: anatomical and functional implications. Trends Neurosci18: 22-29. [PMID:7535487]

38. Mansour A, Thompson RC, Akil H, Watson SJ. (1993) Delta opioid receptor mRNA distribution in the brain: comparison to delta receptor binding and proenkephalin mRNA. J Chem Neuroanat6: 351-362. [PMID:8142072]

39. Martin M, Matifas A, Maldonado R, Kieffer BL. (2003) Acute antinociceptive responses in single and combinatorial opioid receptor knockout mice: distinct mu, delta and kappa tones. Eur J Neurosci17: 701-708. [PMID:12603260]

40. Mennicken F, Zhang J, Hoffert C, Ahmad S, Beaudet A, O'Donnell D. (2003) Phylogenetic changes in the expression of delta opioid receptors in spinal cord and dorsal root ganglia. J Comp Neurol465: 349-360. [PMID:12966560]

41. Mosberg HI, Hurst R, Hruby VJ, Gee K, Yamamura HI, Galligan JJ, Burks TF. (1983) Bis-penicillamine enkephalins possess highly improved specificity toward delta opioid receptors. Proc. Natl. Acad. Sci. U.S.A.80 (19): 5871-4. [PMID:6310598]

42. Neilan CL, Akil H, Woods JH, Traynor JR. (1999) Constitutive activity of the delta-opioid receptor expressed in C6 glioma cells: identification of non-peptide delta-inverse agonists. Br J Pharmacol128: 556-562. [PMID:10516632]

43. Neumeyer JL, Zhang B, Zhang T, Sromek AW, Knapp BI, Cohen DJ, Bidlack JM. (2012) Synthesis, binding affinity, and functional in vitro activity of 3-benzylaminomorphinan and 3-benzylaminomorphine ligands at opioid receptors. J. Med. Chem.55 (8): 3878-90. [PMID:22439881]

44. Pan YZ, Li DP, Chen SR, Pan HL. (2002) Activation of delta-opioid receptors excites spinally projecting locus coeruleus neurons through inhibition of GABAergic inputs. J Neurophysiol88: 2675-2683. [PMID:12424303]

45. Payza K. (2003) Binding and activity of opioid ligands at the cloned human delta, mu and kappa receptors. in The Delta Receptor Edited by Chang KJ CRC Press. 261-275 [ISBN:0824740319]

46. Peckys D, Landwehrmeyer GB. (1999) Expression of mu, kappa, and delta opioid receptor messenger RNA in the human CNS: a 33P in situ hybridization study. Neuroscience88: 1093-1135. [PMID:10336124]

47. Pol O, Palacio JR, Puig MM. (2003) The expression of delta- and kappa-opioid receptor is enhanced during intestinal inflammation in mice. J Pharmacol Exp Ther306: 455-462. [PMID:12724348]

48. Portoghese PS, Sultana M, Takemori AE. (1988) Naltrindole, a highly selective and potent non-peptide delta opioid receptor antagonist. Eur. J. Pharmacol.146 (1): 185-6. [PMID:2832195]

49. Poulain R, Horvath D, Bonnet B, Eckhoff C, Chapelain B, Bodinier MC, Déprez B. (2001) From hit to lead. Combining two complementary methods for focused library design. Application to mu opiate ligands. J. Med. Chem.44 (21): 3378-90. [PMID:11585443]

50. Quock RM, Hosohata Y, Knapp RJ, Burkey TH, Hosohata K, Zhang X, Rice KC, Nagase H, Hruby VJ, Porreca F, Roeske WR, Yamamura HI. (1997) Relative efficacies of delta-opioid receptor agonists at the cloned human delta-opioid receptor. Eur J Pharmacol326: 101-104. [PMID:9178661]

51. Raynor K, Kong H, Chen Y, Yasuda K, Yu L, Bell GI, Reisine T. (1994) Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors. Mol Pharmacol45: 330-334. [PMID:8114680]

52. Rios CD, Jordan BA, Gomes I, Devi LA. (2001) G-protein-coupled receptor dimerization: modulation of receptor function. Pharmacol Ther92: 71-87. [PMID:11916530]

53. Salemi S, Aeschlimann A, Reisch N, Jüngel A, Gay RE, Heppner FL, Michel BA, Gay S, Sprott H. (2005) Detection of kappa and delta opioid receptors in skin--outside the nervous system. Biochem Biophys Res Commun338: 1012-1017. [PMID:16263089]

54. Scherrer G, Befort K, Contet C, Becker J, Matifas A, Kieffer BL. (2004) The delta agonists DPDPE and deltorphin II recruit predominantly mu receptors to produce thermal analgesia: a parallel study of mu, delta and combinatorial opioid receptor knockout mice. Eur J Neurosci19: 2239-2248. [PMID:15090050]

55. Schiller PW, Weltrowska G, Nguyen TM, Wilkes BC, Chung NN, Lemieux C. (1993) TIPP[psi]: a highly potent and stable pseudopeptide delta opioid receptor antagonist with extraordinary delta selectivity. J. Med. Chem.36 (21): 3182-7. [PMID:8230106]

56. Schulz R, Eisinger DA, Wehmeyer A. (2004) Opioid control of MAP kinase cascade. Eur J Pharmacol500: 487-497. [PMID:15464054]

57. Sharma SK, Klee WA, Nirenberg M. (1977) Opiate-dependent modulation of adenylate cyclase. Proc Natl Acad Sci U S A74: 3365-3369. [PMID:269396]

58. Simonin F, Befort K, Gaveriaux-Ruff C, Matthes H, Nappey V, Lannes B, Micheletti G, Kieffer B. (1994) The human delta-opioid receptor: genomic organization, cDNA cloning, functional expression, and distribution in human brain. Mol Pharmacol46: 1015-1021. [PMID:7808419]

59. Smith CF, Waldron C, Brook NA. (1988) Opioid receptors in the mouse ileum. Arch Int Pharmacodyn Ther291: 122-131. [PMID:2835021]

60. Sofuoglu M, Portoghese PS, Takemori AE. (1991) Differential antagonism of delta opioid agonists by naltrindole and its benzofuran analog (NTB) in mice: evidence for delta opioid receptor subtypes. J. Pharmacol. Exp. Ther.257 (2): 676-80. [PMID:1851833]

61. Stefano GB, Melchiorri P, Negri L, Hughes TK, Scharrer B. (1992) [D-Ala2]deltorphin I binding and pharmacological evidence for a special subtype of delta opioid receptor on human and invertebrate immune cells. Proc. Natl. Acad. Sci. U.S.A.89 (19): 9316-20. [PMID:1329092]

62. Szekeres PG, Traynor JR. (1997) Delta opioid modulation of the binding of guanosine-5'-O-(3-[35S]thio)triphosphate to NG108-15 cell membranes: characterization of agonist and inverse agonist effects. J Pharmacol Exp Ther283: 1276-1284. [PMID:9400003]

63. Toll L, Berzetei-Gurske IP, Polgar WE, Brandt SR, Adapa ID, Rodriguez L, Schwartz RW, Haggart D, O'Brien A, White A, Kennedy JM, Craymer K, Farrington L, Auh JS. (1998) Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications.

NOTE: This paper is available through the website of the International Narcotics Research Conference, at http://www.inrcworld.org/links2.htm.
. NIDA Res Monogr178: 440-466. [PMID:9686407]

64. Wentland MP, Lou R, Lu Q, Bu Y, Denhardt C, Jin J, Ganorkar R, VanAlstine MA, Guo C, Cohen DJ et al.. (2009) Syntheses of novel high affinity ligands for opioid receptors. Bioorg. Med. Chem. Lett.19 (8): 2289-94. [PMID:19282177]

65. Xie Z, Bhushan RG, Daniels DJ, Portoghese PS. (2005) Interaction of bivalent ligand KDN21 with heterodimeric delta-kappa opioid receptors in human embryonic kidney 293 cells. Mol Pharmacol68: 1079-1086. [PMID:16006595]

66. Yaksh TL, Noueihed R. (1985) The physiology and pharmacology of spinal opiates. Annu Rev Pharmacol Toxicol25: 433-462. [PMID:2988422]

67. Yasuda K, Raynor K, Kong H, Breder CD, Takeda J, Reisine T, Bell GI. (1993) Cloning and functional comparison of κ and δ opioid receptors from mouse brain. Proc. Natl. Acad. Sci. U.S.A.90: 6736-6740. [PMID:8393575]

68. Zaki PA, Bilsky EJ, Vanderah TW, Lai J, Evans CJ, Porreca F. (1996) Opioid receptor types and subtypes: the delta receptor as a model. Annu Rev Pharmacol Toxicol36: 379-401. [PMID:8725395]

69. Zhu Y, Hsu MS, Pintar JE. (1998) Developmental expression of the mu, kappa, and delta opioid receptor mRNAs in mouse. J Neurosci18: 2538-2549. [PMID:9502813]

70. Zhu Y, King MA, Schuller AG, Nitsche JF, Reidl M, Elde RP, Unterwald E, Pasternak GW, Pintar JE. (1999) Retention of supraspinal delta-like analgesia and loss of morphine tolerance in delta opioid receptor knockout mice. Neuron24: 243-252. [PMID:10677041]

71. Zhu Y, Pintar JE. (1998) Expression of opioid receptors and ligands in pregnant mouse uterus and placenta. Biol Reprod59: 925-932. [PMID:9746745]

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: δ receptor. Last modified on 27/05/2014. Accessed on 26/07/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=317.

Contact us | Print | Back to top | Help
Copyright © 2014 IUPHAR