Gene and Protein Information
class A G protein-coupled receptor
Species	TM	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Human	7	372	1p35.3	OPRD1	opioid receptor delta 1	46,88
Mouse	7	372	4 64.78 cM	Oprd1	opioid receptor, delta 1	26,44,103
Rat	7	372	5q36	Oprd1	opioid receptor, delta 1	1

Previous and Unofficial Names

DOP | DOR | OP1 | Delta receptor | DOR-1 | DOPr | opioid receptor

Database Links
Specialist databases
GPCRdb	oprd_human (Hs), oprd_mouse (Mm), oprd_rat (Rn)
Other databases
Alphafold	P41143 (Hs), P32300 (Mm), P33533 (Rn)
ChEMBL Target	CHEMBL236 (Hs), CHEMBL3222 (Mm), CHEMBL269 (Rn)
DrugBank Target	P41143 (Hs)
Ensembl Gene	ENSG00000116329 (Hs), ENSMUSG00000050511 (Mm), ENSRNOG00000010531 (Rn)
Entrez Gene	4985 (Hs), 18386 (Mm), 24613 (Rn)
Human Protein Atlas	ENSG00000116329 (Hs)
KEGG Gene	hsa:4985 (Hs), mmu:18386 (Mm), rno:24613 (Rn)
OMIM	165195 (Hs)
Pharos	P41143 (Hs)
RefSeq Nucleotide	NM_000911 (Hs), NM_013622 (Mm), NM_012617 (Rn)
RefSeq Protein	NP_000902 (Hs), NP_038650 (Mm), NP_036749 (Rn)
SynPHARM	3818 (in complex with naltrindole) 3817 (in complex with naltrindole)
UniProtKB	P41143 (Hs), P32300 (Mm), P33533 (Rn)
Wikipedia	OPRD1 (Hs)

Selected 3D Structures
	Description:  Structure of the delta opioid receptor bound to naltrindole PDB Id:  4EJ4 Ligand:  naltrindole Resolution:  3.4Å Species:  Mouse References:  35
	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
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

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 Hs Agonist 9.4 pKd 91 ⤷ pKd 9.4 (Kd 4.5x10-10 M) [91] [3H]DPDPE Hs Full agonist 8.9 pKd 2 ⤷ pKd 8.9 [2] [3H]deltorphin II Hs Full agonist 8.7 pKd 10 ⤷ pKd 8.7 [10] UFP-512 Hs Agonist 10.2 pKi 95 ⤷ pKi 10.2 [95] Description: Measuring displacement of [3H]-diprenorphine in vitro AZD7268 Hs Agonist 9.5 pKi 66 ⤷ pKi 9.5 (Ki 3x10-10 M) [66] BW373U86 Hs Agonist 9.5 pKi 50 ⤷ pKi 9.5 (Ki 3.2x10-10 M) [50] DSLET Hs Full agonist 9.3 pKi 93 ⤷ pKi 9.3 [93] [3H]diprenorphine Hs Full agonist 9.3 pKi 3,93 ⤷ pKi 9.3 (Ki 5.01x10-10 M) [3,93] diprenorphine Hs Full agonist 9.3 pKi 93 ⤷ pKi 9.3 [93] DADLE Hs Full agonist 9.2 pKi 93 ⤷ pKi 9.2 (Ki 6.3x10-10 M) [93] (-)-cyclazocine Hs Partial agonist 9.1 pKi 93 ⤷ pKi 9.1 [93] DADLE Mm Full agonist 9.1 pKi 79 ⤷ pKi 9.1 [79] ADL5859 Hs Agonist 9.1 pKi 50 ⤷ pKi 9.1 (Ki 8.4x10-10 M) [50] (-)-bremazocine Hs Full agonist 9.0 pKi 93 ⤷ pKi 9.0 [93] β-endorphin {Sp: Human} Mm Full agonist 9.0 pKi 79 ⤷ pKi 9.0 [79] DPDPE Hs Full agonist 8.8 pKi 65,93 ⤷ pKi 8.8 [65,93] deltorphin II Hs Full agonist 8.8 pKi 93 ⤷ pKi 8.8 [93] etorphine Hs Full agonist 8.8 pKi 93 ⤷ pKi 8.8 (Ki 1.58x10-9 M) [93] [D-Ala2]deltorphin II Hs Full agonist 8.8 pKi 24 ⤷ pKi 8.8 [24] BU08028 Hs Partial agonist 8.8 pKi 43 ⤷ pKi 8.8 (Ki 1.59x10-9 M) [43] BW373U86 Rn Agonist 8.7 pKi 13 ⤷ pKi 8.7 (Ki 1.8x10-9 M) [13] [Leu]enkephalin {Sp: Human, Mouse, Rat} Hs Full agonist 8.7 pKi 93 ⤷ pKi 8.7 [93] DSTBULET Hs Full agonist 8.6 pKi 20 ⤷ pKi 8.6 (Ki 2.81x10-9 M) [20] ADL5747 Hs Agonist 8.6 pKi 51 ⤷ pKi 8.6 (Ki 2.7x10-9 M) [51] ethylketocyclazocine Hs Full agonist 8.5 pKi 93 ⤷ pKi 8.5 (Ki 3.16x10-9 M) [93] deltorphin II Mm Full agonist 8.5 pKi 79 ⤷ pKi 8.5 [79] carfentanil 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} Mm Full agonist 8.4 pKi 79 ⤷ pKi 8.4 [79] dynorphin A-(1-8) {Sp: Human, Mouse, Rat} Hs Partial agonist 8.4 pKi 93 ⤷ pKi 8.4 [93] DSLET Mm Full agonist 8.3 pKi 79 ⤷ pKi 8.3 [79] β-endorphin {Sp: Human} Hs Full agonist 8.3 pKi 93 ⤷ pKi 8.3 [93] SRI22141 Hs Agonist 8.3 pKi 54 ⤷ pKi 8.3 (Ki 5.1x10-9 M) [54] Description: Binding affinity nalmefene Hs Partial agonist 8.1 pKi 93 ⤷ pKi 8.1 [93] tramadol Hs Agonist 8.0 pKi 98 ⤷ pKi 8.0 (Ki 9.4x10-9 M) [98] Description: Displacement of the delta antagonist naltrindole from the delta receptor expressed in CHO cells. dynorphin-(1-11) Hs Full agonist 8.0 pKi 93 ⤷ pKi 8.0 [93] DPDPE Mm Full agonist 7.9 pKi 79 ⤷ pKi 7.9 [79] dynorphin A-(1-13) {Sp: Human, Mouse, Rat} Hs Full agonist 7.8 pKi 93 ⤷ pKi 7.8 [93] dynorphin B {Sp: Human, Mouse, Rat} Hs Full agonist 7.8 pKi 93 ⤷ pKi 7.8 [93] cebranopadol Hs Agonist 7.7 pKi 55 ⤷ pKi 7.7 (Ki 1.8x10-8 M) [55] Description: Radioligand binding assay hydromorphone Hs Agonist 7.4 pKi 97 ⤷ pKi 7.4 (Ki 3.8x10-8 M) [97] dynorphin A {Sp: Human, Mouse, Rat} Hs Full agonist 7.4 pKi 93 ⤷ pKi 7.4 [93] nalorphine Hs Partial agonist 7.4 pKi 93 ⤷ pKi 7.4 [93] (-)-pentazocine Hs Full agonist 7.3 pKi 93 ⤷ pKi 7.3 [93] PN6047 Hs Biased agonist 7.3 pKi 16 ⤷ pKi 7.3 [16] SNC80 Hs Full agonist 7.2 pKi 12,78 ⤷ pKi 7.2 [12,78] normorphine Hs Full agonist 7.1 pKi 93 ⤷ pKi 7.1 [93] AR-M1000390 Hs Agonist 7.0 pKi 61 ⤷ pKi 7.0 (Ki 1.06x10-7 M) [61] (-)-methadone Hs Full agonist 6.9 pKi 93 ⤷ pKi 6.9 [93] morphine Hs Full agonist 6.9 pKi 93 ⤷ pKi 6.9 [93] fentanyl Hs Full agonist 6.8 pKi 93 ⤷ pKi 6.8 [93] bilorphin Hs Agonist 6.7 pKi 19 ⤷ pKi 6.7 (Ki 1.9x10-7 M) [19] dihydromorphine Hs Full agonist 6.7 pKi 93 ⤷ pKi 6.7 [93] etonitazene Hs Full agonist 6.7 pKi 93 ⤷ pKi 6.7 [93] nalbuphine Hs Partial agonist 6.2 pKi 97 ⤷ pKi 6.2 (Ki 5.8x10-7 M) [97] endomorphin-1 {Sp: Human} Hs Full agonist 6.1 pKi 33 ⤷ pKi 6.1 [33] SCH221510 Hs Agonist 5.5 pKi 94 ⤷ pKi 5.5 (Ki 2.854x10-6 M) [94] Description: Radioligand binding assay oxycodegol Hs Agonist 5.4 pKi 64 ⤷ pKi 5.4 (Ki 4.15x10-6 M) [64] Description: Competitive membrane binding assay measuring displacement [3H]DPDPE from human δ receptors expressed by CHO cells. SRI22141 Hs Agonist 8.9 pEC50 54 ⤷ pEC50 8.9 (EC50 1.3x10-9 M) [54] Description: Potency in a 35S-GTPγS assay atoxifent Hs Agonist 8.7 pEC50 96 ⤷ pEC50 8.7 (EC50 2.18x10-9 M) [96] AR-M1000390 Hs Agonist 9.1 pIC50 4 ⤷ pIC50 9.1 (IC50 8.9x10-10 M) [4] TAN-67 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} Mm Full agonist 8.0 pIC50 103 ⤷ pIC50 8.0 [103] [Met]enkephalin {Sp: Human, Mouse, Rat} Mm Full agonist 7.4 pIC50 103 ⤷ pIC50 7.4 [103] ethylketocyclazocine Mm Full agonist 6.2 pIC50 103 ⤷ pIC50 6.2 [103] pethidine Hs Agonist <5.0 pIC50 76 ⤷ pIC50 <5.0 (IC50 >1x10-5 M) [76]
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 [93]. 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 [71]. 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 [83]. 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 [68]. In [68] 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 [97].

Antagonists
Key to terms and symbols	View all chemical structures	Click column headers to sort
Ligand Sp. Action Value Parameter Reference [3H]naltrindole Rn Antagonist 10.4 pKd 102 ⤷ pKd 10.4 (Kd 3.7x10-11 M) [102] naltriben Mm Antagonist 10.9 pKi 79 ⤷ pKi 10.9 [79] naltrindole Mm Antagonist 10.7 pKi 79 ⤷ pKi 10.7 [79] naltriben Hs Antagonist 10.0 pKi 90,93 ⤷ pKi 10.0 (Ki 1x10-10 M) [90,93] naltriben Rn Inverse agonist 10.0 pKi 67 ⤷ pKi 10.0 [67] UFP-505 Hs Antagonist 9.8 pKi 21-22 ⤷ pKi 9.8 [21-22] naltrindole Hs Antagonist 9.7 pKi 75,93 ⤷ pKi 9.7 [75,93] BNTX Mm Antagonist 9.2 pKi 79 ⤷ pKi 9.2 [79] naldemedine Hs Antagonist 9.0 pKi 40 ⤷ pKi 9.0 (Ki 9.1x10-10 M) [40] TIPPψ Hs Inverse agonist 9.0 pKi 85,93 ⤷ pKi 9.0 [85,93] quadazocine Hs Antagonist 8.9 pKi 93 ⤷ pKi 8.9 [93] eluxadoline Rn Antagonist 8.9 pKi 8 ⤷ pKi 8.9 (Ki 1.3x10-9 M) [8] BNTX Rn Inverse agonist 8.7 pKi 67 ⤷ pKi 8.7 [67] samidorphan Hs Antagonist 8.6 pKi 99 ⤷ pKi 8.6 (Ki 2.6x10-9 M) [99] BNTX Hs Antagonist 8.4 pKi 93 ⤷ pKi 8.4 [93] nor-binaltorphimine Hs Antagonist 8.2 pKi 93 ⤷ pKi 8.2 [93] naltrexone Hs Antagonist 8.0 pKi 93 ⤷ pKi 8.0 [93] alvimopan Hs Antagonist 7.9 pKi 49 ⤷ pKi 7.9 (Ki 1.2x10-8 M) [49] β-FNA Hs Antagonist 7.9 pKi 93 ⤷ pKi 7.9 [93] naloxone Mm Antagonist 7.8 pKi 79 ⤷ pKi 7.8 [79] AT-076 Hs Antagonist 7.7 pKi 93,105 ⤷ pKi 7.7 (Ki 1.96x10-8 M) [93,105] Description: Radioligand binding assay ICI 174,864 Rn Inverse agonist 7.4 pKi 67 ⤷ pKi 7.4 [67] naloxone Hs Antagonist 7.2 pKi 93 ⤷ pKi 7.2 [93] LY2456302 Hs Antagonist 6.8 pKi 81 ⤷ pKi 6.8 (Ki 1.55x10-7 M) [81] naltrexone Mm Antagonist 6.8 pKi 79 ⤷ pKi 6.8 [79] NFP Hs Antagonist 6.8 pKi 106 ⤷ pKi 6.8 (Ki 1.57x10-7 M) [106] Description: In a competitive radioligand membrane binding assay measuring displacement of [3H]diprenorphine by NFP from δ receptor expressed in CHO cells. CTAP Hs Antagonist 6.4 pKi 93 ⤷ pKi 6.4 [93] methylnaltrexone Hs Antagonist 6.1 pKi 97 ⤷ pKi 6.1 (Ki 9x10-7 M) [97] zyklophin Hs Antagonist <5.0 pKi 70 ⤷ pKi <5.0 (Ki >1x10-5 M) [70] nor-binaltorphimine Mm Antagonist 6.7 pIC50 103 ⤷ pIC50 6.7 [103] naloxone Mm Antagonist 6.2 pIC50 103 ⤷ pIC50 6.2 [103] NMRA-140 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 [67]. 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 [56].

Allosteric Modulators
Key to terms and symbols	View all chemical structures	Click column headers to sort
Ligand Sp. Action Value Parameter Reference BMS-986187 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 [80] 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] Hs Binding 5.6 pKi 77 ⤷ pKi 5.6 (Ki 2.47x10-6 M) [77] Description: Receptor binding in a radioligand displacement assay using [3H]DADLE as tracer.

Immuno Process Associations

Immuno Process:  Cytokine production & signalling

Primary Transduction Mechanisms
Transducer	Effector/Response
Gi/Go family	Adenylyl 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:  42,48,57,86

Tissue Distribution
Skin. Species:  Human Technique:  RT-PCR and Immunohistochemistry. References:  82
Immune cells. Species:  Human Technique:  RT-PCR. References:  31
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:  109
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:  107
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:  74,84
CNS: cortex, olfactory bulb, olfactory tubercle, caudate putamen, nucleus accumbens, amygdala. Species:  Mouse Technique:  Radioligand binding. References:  34,45
Intestine. Species:  Mouse Technique:  RT-PCR. References:  73
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:  7,60
Ear: cochlea. Species:  Rat Technique:  RT-PCR and immunocytochemistry. References:  41
CNS: superficial layers (laminae I and II) of the dorsal horn of the spinal cord. Species:  Rat Technique:  Radioligand binding. References:  5
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
Tissue Distribution Comments
Studies of the distribution of δ opioid receptors in humans has been limited to autoradiography and in situ hybridisation analysis [7,72]. 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 [63]. 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 [108]. For a review of δ opioid receptor expression in the rat see [59].

Expression Datasets
Show »« Hide 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:  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:  89
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:  87
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:  92

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:  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:  58,69
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 [17,48,101]

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:  28,108
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:  62
δ opioid receptor knockout mice exhibit modified morphine tolerance. Species:  Mouse Tissue:  Technique:  Gene targeting in embryonic stem cells. References:  108
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

Mouse data from MGI

Show »« Hide 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 [6,28,100,104]. δ receptors have also been proposed to interact with μ receptors (for review see [104]). 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 [83]. 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].