NOP receptor | Opioid receptors | IUPHAR/BPS Guide to PHARMACOLOGY

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NOP receptor

Target id: 320

Nomenclature: NOP 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 NOP receptor in GtoImmuPdb

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 370 20q13.33 OPRL1 opioid related nociceptin receptor 1 63
Mouse 7 367 2 H2-4 Oprl1 opioid receptor-like 1 72
Rat 7 367 3q43 Oprl1 opioid related nociceptin receptor 1 9,87
Previous and Unofficial Names
OP4 | N/OFQ receptor | KOR-3 | NOCIR | kappa3-related opioid receptor | MOR-C | nociceptin receptor ORL1 | XOR1 | NOP-r | nociceptin/orphanin FQ receptor | NOPr
Database Links
Specialist databases
GPCRDB oprx_human (Hs), oprx_mouse (Mm), oprx_rat (Rn)
Other databases
ChEMBL Target
Ensembl Gene
Entrez Gene
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 N/OFQ Opioid Receptor in Complex with a Peptide Mimetic
PDB Id:  4EA3
Ligand:  compound 24 [PMID: 16451050]
Resolution:  3.01Å
Species:  Human
References:  81
Natural/Endogenous Ligands
nociceptin/orphanin FQ {Sp: Human, Mouse, Rat}

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
UFP-102 Hs Full agonist 10.7 pKd 15
pKd 10.7 [15]
[3H]Leu-N/OFQ Hs Full agonist 10.2 pKd 54
pKd 10.2 (Kd 6x10-11 M) [54]
[3H]N/OFQ Hs Full agonist 9.8 – 10.2 pKd 23,61
pKd 9.8 – 10.2 (Kd 1.5x10-10 – 6.3x10-11 M) [23,61]
[3H]Tyr14-N/OFQ Mm Full agonist 10.0 pKd 1
pKd 10.0 [1]
[(pF)Phe4]N/OFQ-(1-13)-NH2 Hs Full agonist 10.8 – 11.3 pKi 8,32
pKi 10.8 – 11.3 [8,32]
N/OFQ-NH2 Hs Full agonist 10.4 pKi 54
pKi 10.4 [54]
PWT2-N/OFQ Hs Agonist 10.3 pKi 74
pKi 10.3 [74]
N/OFQ-(1-13)-NH2 Hs Full agonist 10.1 – 10.4 pKi 8,30,54,70
pKi 10.1 – 10.4 [8,30,54,70]
nociceptin/orphanin FQ {Sp: Human, Mouse, Rat} Hs Full agonist 9.7 – 10.4 pKi 1,8,70
pKi 9.7 – 10.4 [1,8,70]
(R)-Ro65-6570 Hs Agonist 9.6 pKi 88
pKi 9.6 [88]
Ac-RYYRWK-NH2 Hs Partial agonist 9.1 – 10.0 pKi 23,54
pKi 9.1 – 10.0 (Ki 7.1x10-10 – 1x10-10 M) [23,54]
SCH221510 Hs Agonist 9.5 pKi 85
pKi 9.5 (Ki 3x10-10 M) [85]
Description: Radioligand binding assay
[Arg14Lys15]N/OFQ Hs Full agonist 9.5 pKi 69
pKi 9.5 [69]
Ro64-6198 Hs Full agonist 9.4 pKi 40,89
pKi 9.4 [40,89]
nociceptin/orphanin FQ {Sp: Human, Mouse, Rat} Mm Full agonist 9.4 pKi 23
pKi 9.4 [23]
SCH221510 Rn Agonist 9.4 pKi 85
pKi 9.4 (Ki 4.2x10-10 M) [85]
Description: Radioligand binding assay
Ac-RYYRWK-NH2 Mm Partial agonist 9.2 pKi 23
pKi 9.2 [23]
[F/G]N/OFQ-(1-13)-NH2 Hs Partial agonist 9.2 pKi 54
pKi 9.2 [54]
cebranopadol Hs Agonist 9.1 pKi 47
pKi 9.1 (Ki 9x10-10 M) [47]
Description: Radioligand binding assay
cebranopadol Rn Agonist 9.0 pKi 47
pKi 9.0 (Ki 1x10-9 M) [47]
Description: Radioligand binding assay
Ac-RYYRIK-NH2 Hs Partial agonist 8.8 – 9.1 pKi 23,54
pKi 8.8 – 9.1 (Ki 1.5x10-9 – 7.9x10-10 M) [23,54]
AT-403 Hs Agonist 9.0 pKi 3
pKi 9.0 (Ki 1.1x10-9 M) [3]
SCH221510 Mm Agonist 8.9 pKi 85
pKi 8.9 (Ki 1.15x10-9 M) [85]
Description: Radioligand binding assay
Ac-RYYRIK-NH2 Mm Partial agonist 8.8 pKi 23
pKi 8.8 [23]
SCH486757 Hs Agonist 8.3 pKi 55
pKi 8.3 (Ki 4.6x10-9 M) [55]
Description: Radioligand binding assay
BU08028 Hs Partial agonist 8.1 pKi 44
pKi 8.1 (Ki 8.46x10-9 M) [44]
SR16835 Hs Agonist 7.9 pKi 83
pKi 7.9 (Ki 1.14x10-8 M) [83]
Description: Radioligand binding assay
[(pF)Phe4]N/OFQ-(1-13)-NH2 Hs Agonist 10.1 pEC50 32
pEC50 10.1 [32]
Description: Stimulation of GTP-γ35S binding
nociceptin/orphanin FQ {Sp: Human, Mouse, Rat} Hs Agonist 8.4 – 9.8 pEC50 23
pEC50 8.4 – 9.8 [23]
UFP-112 Hs Full agonist 8.4 – 9.7 pEC50 14,75
pEC50 8.4 – 9.7 [14,75]
PWT2-N/OFQ Hs Agonist 8.8 pEC50 74
pEC50 8.8 [74]
Description: Stimulation of GTP-γ35S binding
Ac-RYYRWK-NH2 Hs Agonist 8.7 pEC50 23
pEC50 8.7 (EC50 2.1x10-9 M) [23]
SCH221510 Hs Agonist 7.9 pEC50 85
pEC50 7.9 (EC50 1.2x10-8 M) [85]
Description: Stimulation of GTP-γ35S binding
cebranopadol Hs Agonist 7.9 pEC50 47
pEC50 7.9 (EC50 1.3x10-8 M) [47]
Description: Stimulation of GTP-γ35S binding
Ro64-6198 Hs Agonist 7.4 pEC50 89
pEC50 7.4 [89]
Description: Stimulation of GTPγ35S binding
(R)-Ro65-6570 Hs Agonist 7.4 pEC50 88
pEC50 7.4 [88]
Description: Stimulation of GTP-γ35S binding
SR16835 Hs Agonist 7.3 pEC50 83
pEC50 7.3 (EC50 4.61x10-8 M) [83]
Description: Stimulation of GTP-γ35S binding
SCH486757 Hs Agonist 7.1 pEC50 55
pEC50 7.1 (EC50 7.9x10-8 M) [55]
Description: Stimulation of GTP-γ35S binding
Ac-RYYRIK-NH2 Hs Agonist 5.1 pEC50 23
pEC50 5.1 [23]
Description: Stimulation of GTP-γ35S binding
View species-specific agonist tables
Agonist Comments
The above affinities are based on the use of radiolabelled N/OFQ to bind to membrane preparations from CHO cells containing the NOP receptors. This represents a high affinity binding conformation in the absence of Na+ and GTP, and low affinity values are not available. The Ki in intact cells, or in the presence of Na+ and GTP analogues can be different and multiple affinity sites have been observed.

Discrimination of full or partial agonism is very dependent on the level of receptor expression and on the assay used to monitor agonist effects. For instance [Phe1ψ(CH2-NH)Gly2]NC(1-13)NH2, the first "antagonist" reported [31], has antagonist activity in the guinea pig ileum and mouse vas deferens, but partial agonist activity in transfected cells, and full agonist activity in vivo. The identification of agonist activity in the table is largely based on the ability to stimulate GTPγS binding in cell lines expressing cloned human NOP receptors and in some instances smooth muscle bioassays such as mouse or rat vas deferens. Agents giving 85% or greater stimulation than that given by N/OFQ have been characterized as Full Agonists [23,54]. Results may be different in brain membranes. In vivo and smooth muscle bioassay results may also be different and depend upon the assay performed.

Biased Agonists
There are have been two publications discussing biased agonism for the NOP receptor [16,48]. In each case compounds with less than 100% efficacy with respect to G protein coupling appeared to be ineffective for β-arrestin coupling. Furthermore, potencies of agonists for the NOP receptor/β-arrestin interaction were systematically lower that those measured for the NOP receptor/G protein interaction in both publications.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
UFP-101 Hs Antagonist 10.2 pKi 12
pKi 10.2 [12]
LY2940094 Hs Antagonist 10.0 pKi 82
pKi 10.0 (Ki 1x10-10 M) [82]
compound 24 [PMID: 16451050] Hs Antagonist 9.6 pKi 25
pKi 9.6 (Ki 2.4x10-10 M) [25]
SB 612111 Hs Antagonist 9.2 – 9.5 pKi 80,91
pKi 9.2 – 9.5 [80,91]
AT-076 Hs Antagonist 8.8 pKi 93
pKi 8.8 (Ki 1.75x10-9 M) [93]
Description: Radioligand binding assay
J-113397 Hs Antagonist 8.7 pKi 71
pKi 8.7 [71]
[Nphe1]N/OFQ-(1-13)-NH2 Hs Antagonist 8.4 pKi 12
pKi 8.4 [12]
JTC-801 Hs Antagonist 8.1 pKi 77
pKi 8.1 [77]
peptide III-BTD Hs Antagonist 7.6 pKi 4
pKi 7.6 [4]
compound 24 [PMID: 16451050] Hs Antagonist 9.6 – 10.0 pIC50 25,28
pIC50 9.6 – 10.0 (IC50 2.7x10-10 – 1x10-10 M) [25,28]
SB 612111 Hs Antagonist 8.2 – 9.7 pIC50 80,91
pIC50 8.2 – 9.7 [80,91]
J-113397 Hs Antagonist 8.3 pIC50 43
pIC50 8.3 [43]
Antagonist Comments
The above affinities ase based on binding to receptors in membrane preparations and represent a rough average from, in some cases, multiple studies.

So far, no inverse agonists have been reported for the NOP receptor.

More details about the pharmacological profile of the NOP receptors and the chemistry of NOP ligands can be found in review articles [10,13,60,92].
Allosteric Modulator Comments
Although no small molecules are considered direct allosteric regulators of the NOP receptor, a number of proteins such as G protein-coupled receptor kinases, β-arrestins and G proteins clearly regulate receptor functions. Furthermore, sodium and guanyl nucleotides can modify the functional NOP complex and G protein interaction. Finally, other G protein-coupled receptors (i.e. the μ opioid receptor [86]) appear to be able to form heterodimers with NOP receptors, potentailly modifying the receptor activity.
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
Potassium channel
Calcium channel
Other - See Comments
Comments:  NOP receptors have been shown to activate MAP kinase and phospholipase C/[Ca2+] [33].
References:  20,23,58,73,84
Secondary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
References: 
Tissue Distribution
Brain: cerebral > hippocampus, cerebellum, striatum.
Species:  Human
Technique:  Radioligand binding and in situ hybridisation.
References:  5,65
CNS: cortex, olfactory bulb, suprachiasmatic nucleus, amygdala, nucleus accumbens, thalamic nuclei, hypothalamus, hippocampus, septum, superior colliculus.
Species:  Mouse
Technique:  Radioligand binding.
References:  17-19,79
CNS
Species:  Rat
Technique:  Radioligand binding and in situ hubridisation.
References:  12,26,66,78
Tissue Distribution Comments
NOP receptors are located both pre- and post-synaptically in various areas of the CNS.

Brain: cingulate, retrosplenial, perirhinal, insular and occipital cortex, anterior and posteromedial cortical amygdaloid nuclei, basolateral amygdaloid nucleus, amygdaloid complex, posterior hippocampus, dorsal endopiriform, central medial thalamic, paraventricular, rhomboid thalamic, suprachiasmatic, ventromedial hypothalamic nuclei, mammillary complex, superficial gray layer of the superior colliculus, locus coeruleus, dorsal raphe nucleus > prefrontal, fronto-parietal, temporal, piriform cortex, dentate gyrus, anterior olfactory nucleus, olfactory tubercle, shell of nucleus accumbens, claustrum, lateral septum, laterodorsal thalamic, medial habenular, subthalamic, reuniens thalamic nuclei, subiculum, periaqueductal grey matter and pons > anterior and medial hippocampus, olfactory bulb, caudate putamen, the core of the nucleus accumbens, medial septum, ventrolateral, ventroposterolateral and mediodorsal thalamic nuclei, lateral and medial geniculate nuclei, hypothalamic area, substantia nigra, ventral tegmentum area and interpedoncular nucleus.

Like the μ opioid receptor, the NOP receptor shows very dense binding in many caudal and rostral regions, but with a notably distinct binding profile. The distinction of labelling in comparison to the classical opioid receptors is most evident in the caudate putamen, where NOP receptors are relatively low. In contrast, structures such as the suprachiasmatic nucleus have an abundant expression of NOP receptors.

Studies of the distribution of NOP receptors in humans have also been limited to autoradiography and in situ hybridisation analysis. NOP receptors in the CNS appear to have a similar distribution in rat and human. It should be noted that NOP receptors appear far sooner and in larger numbers in the developing brain than the other opioid receptors do, suggesting an important role in development [65-66].
For a review of the tissue distribution of this receptor see [62].

Spinal cord: dorsal and ventral horn.

DRG: Found on large, medium, and small dorsal root ganglia neurons.
Expression Datasets

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

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Functional Assays
Measurement of [35S]GTPγS binding in mouse brain preperations.
Species:  Mouse
Tissue:  Brain membranes.
Response measured:  [35S]GTPγS binding.
References:  84
Measurement of musculature contraction of sections of mouse vas deferens following stimulation of the intramural nerves.
Species:  Mouse
Tissue:  Vas deferens.
Response measured:  Inhibition of electrically-evoked contractions.
References:  6,11
Measurement of adrenergic neuromuscular transmission in the rat anococcygeus muscle.
This tissue is selectively sensitive to N/OFQ and does not respond to classical opioid ligands; thus it can be considered a monoreceptor preparation.
Species:  Rat
Tissue:  Anococcygeus muscle.
Response measured:  Inhibition adrenergic motor response to electrical-field stimulation.
References:  34
Measurement of cAMP levels in CHO cells transfected with the rat NOP receptor.
Species:  Rat
Tissue:  CHO cells.
Response measured:  Inhibition of forskolin-stimulated cAMP accumulation.
References:  23
Measurement of Ca2+ channel activity in SH-SY5Y neuroblastoma cells endogenously expressing the NOP receptor.
Species:  Human
Tissue:  SH-SY5Y neuroblastoma cells.
Response measured:  Inhibition of N-type calcium current.
References:  20
Measurement of cAMP levels in BE(2)-C human neuroblastoma cells endogenously expressing the human NOP receptor.
Species:  Human
Tissue:  BE(2)-C neuroblastoma cells.
Response measured:  Inhibition of forskolin-stimulated cAMP accumulation.
References:  50
Measurement of [35S]GTPγS binding in CHO cells transfected with the mouse κ receptor.
Species:  Mouse
Tissue:  CHO cells.
Response measured:  [35S]GTPγS binding.
References:  23,84
Measurement of cAMP levels in CHO cells transfected with the human NOP receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Inhibition of forskolin-stimulated cAMP accumulation.
References:  58
Physiological Functions
Inhibition of electrically-evoked muscle contraction in the vas deferens.
Species:  Mouse
Tissue:  Vas deferens.
References:  6,11
Inhibition of electrically-evoked muscle contraction of the colon.
Species:  Rat
Tissue:  Colon.
References:  56
Inhibition of electrically-evoked muscle contraction in the vas deferens.
Species:  Rat
Tissue:  Vas deferens.
References:  7
Inhibition of glutamate release.
Species:  Rat
Tissue:  Cerebrocortical slices.
References:  67
Inhibition of acetylcholine release.
Species:  Rat
Tissue:  In vivo.
References:  38
NOP agonist-induced anxiogenic activity.
Species:  Rat
Tissue:  In vivo.
References:  24
Inhibition of noradrenaline release.
Species:  Mouse
Tissue:  Cortex slices.
References:  76
Inhibition of glutamate release.
Species:  Rat
Tissue:  Cerebrocortical slices.
References:  67
Inhibition of serotonin release.
Species:  Rat
Tissue:  Neocortex.
References:  53
Contraction of the colon.
Species:  Mouse
Tissue:  Colon.
References:  56
Nociception.
Species:  Mouse
Tissue:  In vivo.
References:  36-37,58-59
NOP agonist-induced anxiolytic activity after i.c.v. or peripheral injection.
Species:  Rat
Tissue:  In vivo.
References:  40
NOP agonist-induced anxiolytic activity after i.c.v. or peripheral injection.
Species:  Mouse
Tissue:  In vivo.
References:  39
NOP agonist-induced cardiovascular depression and water diuretic activity after either i.c.v. or intravenous administration.
Species:  Rat
Tissue:  In vivo.
References:  41-42
Inhibition of opioid antinociception.
Species:  Mouse
Tissue:  In vivo i.c.v. administration
References:  58-59,73
Antinociceptive activity.
Species:  Mouse
Tissue:  In vivo, intrathecal administration
References:  29,90
Inhibition of dopamine release.
Species:  Rat
Tissue:  In vivo, measured by microdialysis
References:  22,45,64
Physiological Functions Comments
Nociception: NOP receptor agonists attenuate opiate-mediated and stress-induced analgesia when administered i.c.v. but have antinociceptive activity when administered intrathecally. Small molecule agonists and antagonists generally have little effect on pain threshold when administered alone systemically in rodents. In chronic pain states systemic administration of small molecule NOP agonists is effective for inhibition of mechanical allodynia. In non-human primates, selective NOP agonists have antinociceptive activity. NOP receptor agonists and antagonists have many behavioural functions not discussed here, for a good review on the topic see [46].
For a review on the functional architecture of the NOP receptor, including information on splice variants, see reference [57].
Physiological Consequences of Altering Gene Expression
Mice lacking the gene coding for the NOP receptor (NOP-/- mice) are viable, breed well and appear to age normally.
NOP receptor knockout mice exhibit insufficient recovery of hearing ability from the adaptation to sound exposure.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  68
NOP receptor knockout mice exhibit facilitation of long-term potentiation and learning abilities.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  49
NOP receptor knockout mice exhibit normal sensitivity to acute nociceptive stimulation but pronociceptive phenotype in some nociceptive tests.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  21,35
NOP receptor knockout mice exhibit an antidepressant phenotype in the forced swimming assay.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  27
NOP receptor knockout mice exhibit a better locomotor performance in the rotarod test and less sensitivity to haloperidol-induced motor depression.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  51-52
NOP receptor knockout mice exhibit attenuation of morphine tolerance and dependence.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  84
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Oprl1tm1Hta Oprl1tm1Hta/Oprl1tm1Hta
involves: 129S4/SvJae * C57BL/6J
MGI:97440  MP:0002735 abnormal chemical nociception PMID: 12814369  9155012 
Oprl1tm1Hta Oprl1tm1Hta/Oprl1tm1Hta
involves: 129S4/SvJae * C57BL/6J
MGI:97440  MP:0002063 abnormal learning/memory/conditioning PMID: 9707118 
Oprl1tm1Hta Oprl1tm1Hta/Oprl1tm1Hta
involves: 129S4/SvJae
MGI:97440  MP:0002734 abnormal mechanical nociception PMID: 16519664 
Oprl1tm1Hta Oprl1tm1Hta/Oprl1tm1Hta
involves: 129S4/SvJae * C57BL/6J
MGI:97440  MP:0002799 abnormal passive avoidance behavior PMID: 9707118 
Oprl1tm1Hta Oprl1tm1Hta/Oprl1tm1Hta
involves: 129S4/SvJae * C57BL/6J
MGI:97440  MP:0001413 abnormal response to new environment PMID: 9707118 
Oprl1tm1Hta Oprl1tm1Hta/Oprl1tm1Hta
involves: 129S4/SvJae * C57BL/6J
MGI:97440  MP:0001463 abnormal spatial learning PMID: 9707118 
Oprl1tm1Hta Oprl1tm1Hta/Oprl1tm1Hta
involves: 129S4/SvJae * C57BL/6J
MGI:97440  MP:0001968 abnormal touch/ nociception PMID: 9155012 
Oprl1tm1Hta Oprl1tm1Hta/Oprl1tm1Hta
involves: 129S4/SvJae * C57BL/6J
MGI:97440  MP:0001982 decreased chemically-elicited antinociception PMID: 9660760 
Oprl1tm1Hta Oprl1tm1Hta/Oprl1tm1Hta
involves: 129S4/SvJae * C57BL/6J
MGI:97440  MP:0003998 decreased thermal nociceptive threshold PMID: 12814369 
Oprl1tm1Hta Oprl1tm1Hta/Oprl1tm1Hta
involves: 129S4/SvJae * C57BL/6J
MGI:97440  MP:0003008 enhanced long term potentiation PMID: 9707118 
Oprl1tm1Hta Oprl1tm1Hta/Oprl1tm1Hta
involves: 129S4/SvJae * C57BL/6J
MGI:97440  MP:0009757 impaired behavioral response to morphine PMID: 11027224 
Oprl1tm1Hta Oprl1tm1Hta/Oprl1tm1Hta
involves: 129S4/SvJae * C57BL/6J
MGI:97440  MP:0001906 increased dopamine level PMID: 15030410 
Oprl1tm1Hta Oprl1tm1Hta/Oprl1tm1Hta
involves: 129S4/SvJae * C57BL/6J
MGI:97440  MP:0004597 increased susceptibility to noise-induced hearing loss PMID: 9155012 
Oprl1tm1Dgen Oprl1tm1Dgen/Oprl1tm1Dgen
involves: 129P2/OlaHsd * C57BL/6
MGI:97440  MP:0002169 no abnormal phenotype detected
Biologically Significant Variants
Type:  Single nucleotide polymorphism
Species:  Human
Description:  SNP rs6010719 is associated with increased PTSD symptoms.
SNP accession: 
References:  2
Type:  Single nucleotide polymorphism
Species:  Human
Description:  SNP rs6010718 is linked with alcoholism
SNP accession: 

References

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1. Adapa ID, Toll L. (1997) Relationship between binding affinity and functional activity of nociceptin/orphanin FQ. Neuropeptides, 31: 403-408. [PMID:9413015]

2. Andero R, Brothers SP, Jovanovic T, Chen YT, Salah-Uddin H, Cameron M, Bannister TD, Almli L, Stevens JS, Bradley B et al.. (2013) Amygdala-dependent fear is regulated by Oprl1 in mice and humans with PTSD. Sci Transl Med, 5 (188): 188ra73. [PMID:23740899]

3. Arcuri L, Novello S, Frassineti M, Mercatelli D, Pisanò CA, Morella I, Fasano S, Journigan BV, Meyer ME, Polgar WE et al.. (2018) Anti-Parkinsonian and anti-dyskinetic profiles of two novel potent and selective nociceptin/orphanin FQ receptor agonists. Br. J. Pharmacol., 175 (5): 782-796. [PMID:29232769]

4. Becker JA, Wallace A, Garzon A, Ingallinella P, Bianchi E, Cortese R, Simonin F, Kieffer BL, Pessi A. (1999) Ligands for kappa-opioid and ORL1 receptors identified from a conformationally constrained peptide combinatorial library. J Biol Chem, 274: 27513-27522. [PMID:10488086]

5. Berthele A, Platzer S, Dworzak D, Schadrack J, Mahal B, Büttner A, Assmus HP, Wurster K, Zieglgänsberger W, Conrad B, Tölle TR. (2003) [3H]-nociceptin ligand-binding and nociceptin opioid receptor mrna expression in the human brain. Neuroscience, 121: 629-640. [PMID:14568023]

6. Berzetei-Gurske IP, Schwartz RW, Toll L. (1996) Determination of activity for nociceptin in the mouse vas deferens. Eur J Pharmacol, 302: R1-R2. [PMID:8791013]

7. Bigoni R, Giuliani S, Calo' G, Rizzi A, Guerrini R, Salvadori S, Regoli D, Maggi CA. (1999) Characterization of nociceptin receptors in the periphery: in vitro and in vivo studies. Naunyn Schmiedebergs Arch Pharmacol, 359: 160-167. [PMID:10208302]

8. Bigoni R, Rizzi D, Rizzi A, Camarda V, Guerrini R, Lambert DG, Hashiba E, Berger H, Salvadori S, Regoli D, Calo' G. (2002) Pharmacological characterisation of [(pX)Phe4]nociceptin(1-13)amide analogues. 1. In vitro studies. Naunyn Schmiedebergs Arch Pharmacol, 365: 442-449. [PMID:12070757]

9. Bunzow JR, Saez C, Mortrud M, Bouvier C, Williams JT, Low M, Grandy DK. (1994) Molecular cloning and tissue distribution of a putative member of the rat opioid receptor gene family that is not μ, δ or κ opioid receptor type. FEBS Lett., 347: 284-288. [PMID:8034019]

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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: NOP receptor. Last modified on 20/02/2018. Accessed on 11/12/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=320.