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. 

Contents

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 opiate receptor-like 1 50
Mouse 7 367 2 H2-4 Oprl1 opioid receptor-like 1 57
Rat 7 367 3q43 Oprl1 opiate receptor-like 1 7,66
Previous and Unofficial Names
LY322
N/OFQ receptor
ORL1
OP4
NOCIR
OOR
KOR-3
LC132 receptor-like
orphanin FQ receptor
kappa3-related opioid receptor
KOR3
LC132
MOR-C
OFQR
Oprl
XOR1
ROR-C
kappa-type 3 opioid receptor
nociceptin receptor
nociceptin receptor ORL1
opiate receptor-like 1
opioid receptor-like
opioid receptor-like 1
orphanin FQ receptor-a
orphanin FQ receptor-b
orphanin FQ receptor-e
peptide receptor
seven transmembrane G protein-coupled receptor
morc
NOP-r
nociceptin/orphanin FQ receptor
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 N/OFQ Opioid Receptor in Complex with a Peptide Mimetic
PDB Id:  4EA3
Ligand:  Banyu Compound-24
Resolution:  3.01Å
Species:  Human
References:  63
Natural/Endogenous Ligands
nociceptin/orphanin FQ {Sp: Human, Mouse, Rat}
Rank order of potency (Human)
N/OFQ (PNOC, Q13519) >> dynorphin A (PDYN, P01213)
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 13
pKd 10.7 [13]
[3H]N/OFQ Hs Full agonist 10.2 pKd 19,49
pKd 10.2 (Kd 6.3x10-11 M) [19,49]
[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 pKi 6
pKi 10.8 [6]
N/OFQ-NH2 Hs Full agonist 10.4 pKi 42
pKi 10.4 [42]
N/OFQ-(1-13)-NH2 Hs Full agonist 10.1 – 10.4 pKi 6,25,42,55
pKi 10.1 – 10.4 [6,25,42,55]
nociceptin/orphanin FQ {Sp: Human, Mouse, Rat} Hs Full agonist 9.7 – 10.4 pKi 6,42,48-49,55
pKi 9.7 – 10.4 [6,42,48-49,55]
Ac-RYYRWK-NH2 Hs Partial agonist 10.0 pKi 42
pKi 10.0 [42]
Ro64-6198 Hs Full agonist 9.6 pKi 33
pKi 9.6 [33]
[Arg14Lys15]N/OFQ Hs Full agonist 9.5 pKi 54
pKi 9.5 [54]
nociceptin/orphanin FQ {Sp: Human, Mouse, Rat} Mm Full agonist 9.4 pKi 20
pKi 9.4 [20]
[F/G]N/OFQ-(1-13)-NH2 Hs Partial agonist 9.2 pKi 42
pKi 9.2 [42]
Ac-RYYRWK-NH2 Mm Partial agonist 9.2 pKi 20
pKi 9.2 [20]
Ac-RYYRIK-NH2 Hs Partial agonist 9.1 pKi 42
pKi 9.1 [42]
Ac-RYYRIK-NH2 Mm Partial agonist 8.8 pKi 20
pKi 8.8 [20]
UFP-112 Hs Full agonist 8.39 – 9.71 pEC50 12,59
pEC50 8.39 – 9.71 [12,59]
Ro64-6198 Hs Agonist 7.45 – 8.51 pEC50 12
pEC50 7.45 – 8.51 [12]
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 receptor, and contain a rough average from, in some cases, multiple studies. 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. Many agents may behave as full agonists or potent partial agonists in cell lines expressing cloned receptors in high concentration, but in other environments they may show only weak agonist activity. The identification of agonist activity in the table is largely based on the ability to stimulate GTPγS binding in cell lines expressing cloned human NOP receptors. Agents giving 85% or greater stimulation than that given by N/OFQ have been characterized as Full Agonists [20,42]. Results may be different in brain membranes. In vivo and smooth muscle bioassay results may also be different and depend upon the assay performed.
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 10
pKi 10.2 [10]
SB 612111 Hs Antagonist 9.5 pKi 67
pKi 9.5 [67]
J-113397 Hs Antagonist 8.7 pKi 56
pKi 8.7 [56]
[Nphe1]N/OFQ-(1-13)-NH2 Hs Antagonist 8.4 pKi 10
pKi 8.4 [10]
JTC-801 Hs Antagonist 8.1 pKi 61
pKi 8.1 [61]
peptide III-BTD Hs Antagonist 7.6 pKi 2
pKi 7.6 [2]
J-113397 Hs Antagonist 8.3 pIC50 36
pIC50 8.3 [36]
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 [8,11,47,68].
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 [65]) 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+] [26].
References:  17,20,45,58,64
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:  3
CNS: cortex, olfactory bulb, suprachiasmatic nucleus, amygdala, nucleus accumbens, thalamic nuclei, hypothalamus, hippocampus, septum, superior colliculus.
Species:  Mouse
Technique:  Radioligand binding.
References:  14-16,62
Brain: outer and medial cortical layers, subiculum, hippocampus, nucleus accumbens > inner cortical layer, pontine nuclei, thalamus, hypothalamus > cerebellum, striatum.
Species:  Rat
Technique:  Rad
References:  23
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.
Spinal cord: dorsal and ventral horn.
Species:  Rat
Technique:  Radioligand binding.
References:  22
Tissue Distribution Comments
Receptor Distribution
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 179-184.
For a review of the tissue distribution of this receptor see 177.

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 [35S]GTPγS binding in CHO cells transfected with the mouse κ receptor.
Species:  Mouse
Tissue:  CHO cells.
Response measured:  [35S]GTPγS binding.
References:  20,64
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:  4,9
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:  27
Measurement of cAMP levels in CHO cells transfected with the human NOR receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Inhibition of forskolin-stimulated cAMP accumulation.
References:  45
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:  20
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:  17
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:  38
Measurement of [35S]GTPγS binding in mouse brain preperations.
Species:  Mouse
Tissue:  Brain membranes.
Response measured:  [35S]GTPγS binding.
References:  64
Physiological Functions
Inhibition of electrically-evoked muscle contraction in the vas deferens.
Species:  Mouse
Tissue:  Vas deferens.
References:  4,9
Inhibition of electrically-evoked muscle contraction of the colon.
Species:  Mouse
Tissue:  Colon.
References:  43
Inhibition of electrically-evoked muscle contraction of the colon.
Species:  Rat
Tissue:  Colon.
References:  43
Inhibition of electrically-evoked muscle contraction in the vas deferens.
Species:  Rat
Tissue:  Vas deferens.
References:  5
Inhibition of glutamate release.
Species:  Rat
Tissue:  Cerebrocortical slices.
References:  52
Inhibition of dopamine release.
Species:  Rat
Tissue:  In vivo.
References:  51
Inhibition of acetylcholine release.
Species:  Rat
Tissue:  In vivo.
References:  31
NOP agonist-induced inhibition of opiate analgesia, and potentially hyperalgesia after ICV injection. Direct hyperalgesic activity is unclear and may be due to stress-induced analgesia from ICV injection. The NOP agonist showed dose-related opposite modulation of nociception after peripheral or intrathecal injection. NOP agonist-induced antinociception or potentaition of morphine antinociception after intrathecal injection has also been reported.
Species:  Mouse
Tissue:  In vivo.
References:  29-30,45-46
NOP agonist-induced anxiolytic activity after ICV or peripheral injection.
Species:  Rat
Tissue:  In vivo.
References:  33
NOP agonist-induced anxiolytic activity after ICV or peripheral injection.
Species:  Mouse
Tissue:  In vivo.
References:  32
NOP agonist-induced anxiogenic activity.
Species:  Rat
Tissue:  In vivo.
References:  21
NOP agonist-induced cardiovascular depression and water diuretic activity after either ICV or intravenous administration.
Species:  Rat
Tissue:  In vivo.
References:  34-35
Inhibition of noradrenaline release.
Species:  Mouse
Tissue:  Cortex slices.
References:  60
Inhibition of glutamate release.
Species:  Rat
Tissue:  Cerebrocortical slices.
References:  52
Inhibition of serotonin release.
Species:  Rat
Tissue:  Neocortex.
References:  41
Physiological Functions Comments
For a review on the functional architecture of the NOP receptor, including information on splice variants, see reference [44].
Physiological Consequences of Altering Gene Expression
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:  18,28
NOP receptor knockout mice exhibit an antidepressant phenotype in the forced swimming assay.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  24
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:  39-40
NOP receptor knockout mice exhibit attenuation of morphine tolerance and dependence.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  64
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:  53
NOP receptor knockout mice exhibit facilitation of long-term potentiation and learning abilities.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  37
Phenotypes, Alleles and Disease Models Mouse data from MGI

Show »

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
Available Assays
DiscoveRx PathHunter® CHO-K1 OPRL1 β-Arrestin Cell Line (Cat no. 93-0264C2)
PathHunter® eXpress OPRL1 CHO-K1 β-Arrestin GPCR Assay (Cat no. 93-0264E2CP0M)
more info

REFERENCES

1. Adapa ID, Toll L. (1997) Relationship between binding affinity and functional activity of nociceptin/orphanin FQ. Neuropeptides31: 403-408. [PMID:9413015]

2. 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 Chem274: 27513-27522. [PMID:10488086]

3. 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. Neuroscience121: 629-640. [PMID:14568023]

4. Berzetei-Gurske IP, Schwartz RW, Toll L. (1996) Determination of activity for nociceptin in the mouse vas deferens. Eur J Pharmacol302: R1-R2. [PMID:8791013]

5. 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 Pharmacol359: 160-167. [PMID:10208302]

6. 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 Pharmacol365: 442-449. [PMID:12070757]

7. 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]

8. Calo G, Guerrini R, Rizzi A, Salvadori S, Burmeister M, Kapusta DR, Lambert DG, Regoli D. (2005) UFP-101, a peptide antagonist selective for the nociceptin/orphanin FQ receptor. CNS Drug Rev11: 97-112. [PMID:16007234]

9. Calo G, Rizzi A, Bogoni G, Neugebauer V, Salvadori S, Guerrini R, Bianchi C, Regoli D. (1996) The mouse vas deferens: a pharmacological preparation sensitive to nociceptin. Eur J Pharmacol311: R3-R5. [PMID:8884244]

10. Calo G, Rizzi A, Rizzi D, Bigoni R, Guerrini R, Marzola G, Marti M, McDonald J, Morari M, Lambert DG, Salvadori S, Regoli D. (2002) [Nphe1,Arg14,Lys15]nociceptin-NH2, a novel potent and selective antagonist of the nociceptin/orphanin FQ receptor. Br J Pharmacol136: 303-311. [PMID:12010780]

11. Calo' G, Bigoni R, Rizzi A, Guerrini R, Salvadori S, Regoli D. (2000) Nociceptin/orphanin FQ receptor ligands. Peptides21: 935-947. [PMID:10998527]

12. Camarda V, Fischetti C, Anzellotti N, Molinari P, Ambrosio C, Kostenis E, Regoli D, Trapella C, Guerrini R, Severo S et al.. (2009) Pharmacological profile of NOP receptors coupled with calcium signaling via the chimeric protein G alpha qi5. Naunyn Schmiedebergs Arch. Pharmacol.379 (6): 599-607. [PMID:19183962]

13. Carrà G, Rizzi A, Guerrini R, Barnes TA, McDonald J, Hebbes CP, Mela F, Kenigs VA, Marzola G, Rizzi D, Gavioli E, Zucchini S, Regoli D, Morari M, Salvadori S, Rowbotham DJ, Lambert DG, Kapusta DR, Calo' G. (2005) [(pF)Phe4,Arg14,Lys15]N/OFQ-NH2 (UFP-102), a highly potent and selective agonist of the nociceptin/orphanin FQ receptor. J Pharmacol Exp Ther312: 1114-1123. [PMID:15509719]

14. Clarke S, Chen Z, Hsu MS, Hill RG, Pintar JE, Kitchen I. (2003) Nociceptin/orphanin FQ knockout mice display up-regulation of the opioid receptor-like 1 receptor and alterations in opioid receptor expression in the brain. Neuroscience117: 157-168. [PMID:12605902]

15. Clarke S, Chen Z, Hsu MS, Pintar J, Hill R, Kitchen I. (2001) Quantitative autoradiographic mapping of the ORL1, mu-, delta- and kappa-receptors in the brains of knockout mice lacking the ORL1 receptor gene. Brain Res906: 13-24. [PMID:11430857]

16. Clarke S, Czyzyk T, Ansonoff M, Nitsche JF, Hsu MS, Nilsson L, Larsson K, Borsodi A, Toth G, Hill R, Kitchen I, Pintar JE. (2002) Autoradiography of opioid and ORL1 ligands in opioid receptor triple knockout mice. Eur J Neurosci16: 1705-1712. [PMID:12431223]

17. Connor M, Yeo A, Henderson G. (1996) The effect of nociceptin on Ca2+ channel current and intracellular Ca2+ in the SH-SY5Y human neuroblastoma cell line. Br J Pharmacol118: 205-207. [PMID:8735615]

18. Depner UB, Reinscheid RK, Takeshima H, Brune K, Zeilhofer HU. (2003) Normal sensitivity to acute pain, but increased inflammatory hyperalgesia in mice lacking the nociceptin precursor polypeptide or the nociceptin receptor. Eur J Neurosci17: 2381-2387. [PMID:12814369]

19. Dooley CT, Houghten RA. (1996) Orphanin FQ: receptor binding and analog structure activity relationships in rat brain. Life Sci.59 (1): PL23-9. [PMID:8684262]

20. Dooley CT, Spaeth CG, Berzetei-Gurske IP, Craymer K, Adapa ID, Brandt SR, Houghten RA, Toll L. (1997) Binding and in vitro activities of peptides with high affinity for the nociceptin/orphanin FQ receptor, ORL1. J Pharmacol Exp Ther283: 735-741. [PMID:9353393]

21. Fernandez F, Misilmeri MA, Felger JC, Devine DP. (2004) Nociceptin/orphanin FQ increases anxiety-related behavior and circulating levels of corticosterone during neophobic tests of anxiety. Neuropsychopharmacology29: 59-71. [PMID:14532912]

22. Florin S, Meunier J, Costentin J. (2000) Autoradiographic localization of [3H]nociceptin binding sites in the rat brain. Brain Res880: 11-16. [PMID:11032985]

23. Foddi MC, Mennini T. (1997) [125I][Tyr14]Orphanin binding to rat brain: evidence for labelling the opioid-receptor-like 1 (ORL1). Neurosci Lett230: 105-108. [PMID:9259475]

24. Gavioli EC, Marzola G, Guerrini R, Bertorelli R, Zucchini S, De Lima TC, Rae GA, Salvadori S, Regoli D, Calo G. (2003) Blockade of nociceptin/orphanin FQ-NOP receptor signalling produces antidepressant-like effects: pharmacological and genetic evidences from the mouse forced swimming test. Eur J Neurosci17: 1987-1990. [PMID:12752799]

25. Guerrini R, Calo G, Rizzi A, Bianchi C, Lazarus LH, Salvadori S, Temussi PA, Regoli D. (1997) Address and message sequences for the nociceptin receptor: a structure-activity study of nociceptin-(1-13)-peptide amide. J. Med. Chem.40 (12): 1789-93. [PMID:9191955]

26. Hawes BE, Graziano MP, Lambert DG. (2000) Cellular actions of nociceptin: transduction mechanisms. Peptides21: 961-967. [PMID:10998529]

27. Ho M, Corbett AD, McKnight AT. (2000) Characterization of the ORL(1) receptor on adrenergic nerves in the rat anococcygeus muscle. Br J Pharmacol131: 349-355. [PMID:10991930]

28. Inoue M, Kawashima T, Takeshima H, Calo G, Inoue A, Nakata Y, Ueda H. (2003) In vivo pain-inhibitory role of nociceptin/orphanin FQ in spinal cord. J Pharmacol Exp Ther305: 495-501. [PMID:12606680]

29. Inoue M, Kobayashi M, Kozaki S, Zimmer A, Ueda H. (1998) Nociceptin/orphanin FQ-induced nociceptive responses through substance P release from peripheral nerve endings in mice. Proc Natl Acad Sci U S A95: 10949-10953. [PMID:9724810]

30. Inoue M, Shimohira I, Yoshida A, Zimmer A, Takeshima H, Sakurada T, Ueda H. (1999) Dose-related opposite modulation by nociceptin/orphanin FQ of substance P nociception in the nociceptors and spinal cord. J Pharmacol Exp Ther291: 308-313. [PMID:10490918]

31. Itoh K, Konya H, Takai E, Masuda H, Nagai K. (1999) Modification of acetylcholine release by nociceptin in conscious rat striatum. Brain Res845: 242-245. [PMID:10536205]

32. Jenck F, Moreau JL, Martin JR, Kilpatrick GJ, Reinscheid RK, Monsma FJ, Nothacker HP, Civelli O. (1997) Orphanin FQ acts as an anxiolytic to attenuate behavioral responses to stress. Proc Natl Acad Sci U S A94: 14854-14858. [PMID:9405703]

33. Jenck F, Wichmann J, Dautzenberg FM, Moreau JL, Ouagazzal AM, Martin JR, Lundstrom K, Cesura AM, Poli SM, Roever S, Kolczewski S, Adam G, Kilpatrick G. (2000) A synthetic agonist at the orphanin FQ/nociceptin receptor ORL1: anxiolytic profile in the rat. Proc Natl Acad Sci U S A97: 4938-4943. [PMID:10758169]

34. Kapusta DR, Burmeister MA, Calo' G, Guerrini R, Gottlieb HB, Kenigs VA. (2005) Functional selectivity of nociceptin/orphanin FQ peptide receptor partial agonists on cardiovascular and renal function. J Pharmacol Exp Ther314: 643-651. [PMID:15855356]

35. Kapusta DR, Kenigs VA. (1999) Cardiovascular and renal responses produced by central orphanin FQ/nociceptin occur independent of renal nerves. Am J Physiol277: R987-R995. [PMID:10516236]

36. Kawamoto H, Ozaki S, Itoh Y, Miyaji M, Arai S, Nakashima H, Kato T, Ohta H, Iwasawa Y. (1999) Discovery of the first potent and selective small molecule opioid receptor-like (ORL1) antagonist: 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1, 3-dihydro-2H-benzimidazol-2-one (J-113397). J. Med. Chem.42: 5061-5063. [PMID:10602690]

37. Manabe T, Noda Y, Mamiya T, Katagiri H, Houtani T, Nishi M, Noda T, Takahashi T, Sugimoto T, Nabeshima T, Takeshima H. (1998) Facilitation of long-term potentiation and memory in mice lacking nociceptin receptors. Nature394: 577-581. [PMID:9707118]

38. Mandyam CD, Altememi GF, Standifer KM. (2000) beta-Funaltrexamine inactivates ORL1 receptors in BE(2)-C human neuroblastoma cells. Eur J Pharmacol402: R1-37. [PMID:10940375]

39. Marti M, Mela F, Fantin M, Zucchini S, Brown JM, Witta J, Di Benedetto M, Buzas B, Reinscheid RK, Salvadori S, Guerrini R, Romualdi P, Candeletti S, Simonato M, Cox BM, Morari M. (2005) Blockade of nociceptin/orphanin FQ transmission attenuates symptoms and neurodegeneration associated with Parkinson's disease. J Neurosci25: 9591-9601. [PMID:16237164]

40. Marti M, Mela F, Veronesi C, Guerrini R, Salvadori S, Federici M, Mercuri NB, Rizzi A, Franchi G, Beani L, Bianchi C, Morari M. (2004) Blockade of nociceptin/orphanin FQ receptor signaling in rat substantia nigra pars reticulata stimulates nigrostriatal dopaminergic transmission and motor behavior. J Neurosci24: 6659-6666. [PMID:15282268]

41. Marti M, Stocchi S, Paganini F, Mela F, De Risi C, Calo' G, Guerrini R, Barnes TA, Lambert DG, Beani L, Bianchi C, Morari M. (2003) Pharmacological profiles of presynaptic nociceptin/orphanin FQ receptors modulating 5-hydroxytryptamine and noradrenaline release in the rat neocortex. Br J Pharmacol138: 91-98. [PMID:12522077]

42. McDonald J, Barnes TA, Okawa H, Williams J, Calo' G, Rowbotham DJ, Lambert DG. (2003) Partial agonist behaviour depends upon the level of nociceptin/orphanin FQ receptor expression: studies using the ecdysone-inducible mammalian expression system. Br J Pharmacol140: 61-70. [PMID:12967935]

43. Menzies JR, Glen T, Davies MR, Paterson SJ, Corbett AD. (1999) In vitro agonist effects of nociceptin and [Phe(1)psi(CH(2)-NH)Gly(2)]nociceptin(1-13)NH(2) in the mouse and rat colon and the mouse vas deferens. Eur J Pharmacol385: 217-223. [PMID:10607879]

44. Meunier J, Mouledous L, Topham CM. (2000) The nociceptin (ORL1) receptor: molecular cloning and functional architecture. Peptides21: 893-900. [PMID:10998522]

45. Meunier J-C, Mollereau C, Toll L, Suaudeau C, Moisand C, Alvinerie P, Butour JL, Guillemot JC, Ferrara P, Monsarrat B et al.. (1995) Isolation and structure of the endogenous agonist of opioid receptor-like ORL-1 receptor. Nature377: 532-535. [PMID:7566152]

46. Mogil JS, Grisel JE, Zhangs G, Belknap JK, Grandy DK. (1996) Functional antagonism of mu-, delta- and kappa-opioid antinociception by orphanin FQ. Neurosci Lett214: 131-134. [PMID:8878101]

47. Mogil JS, Pasternak GW. (2001) The molecular and behavioral pharmacology of the orphanin FQ/nociceptin peptide and receptor family. Pharmacol Rev53: 381-415. [PMID:11546835]

48. Molinari S, Camarda V, Rizzi A, Marzola G, Salvadori S, Marzola E, Molinari P, McDonald J, Ko MC, Lambert DG et al.. (2013) [Dmt1]N/OFQ(1-13)-NH2: a potent nociceptin/orphanin FQ and opioid receptor universal agonist. Br. J. Pharmacol.168 (1): 151-62. [PMID:22827708]

49. Mollereau C, Moisand C, Butour JL, Parmentier M, Meunier JC. (1996) Replacement of Gln280 by His in TM6 of the human ORL1 receptor increases affinity but reduces intrinsic activity of opioids. FEBS Lett395: 17-21. [PMID:8849681]

50. Mollereau C, Parmentier M, Mailleux P, Butour JL, Moisand C, Chalon P, Caput D, Vassart G, Meunier JC. (1994) ORL1, a novel member of the opioid receptor family. Cloning, functional expression and localization. FEBS Lett341: 33-38. [PMID:8137918]

51. Murphy NP, Ly HT, Maidment NT. (1996) Intracerebroventricular orphanin FQ/nociceptin suppresses dopamine release in the nucleus accumbens of anaesthetized rats. Neuroscience75: 1-4. [PMID:8923516]

52. Nicol B, Lambert DG, Rowbotham DJ, Smart D, McKnight AT. (1996) Nociceptin induced inhibition of K+ evoked glutamate release from rat cerebrocortical slices. Br J Pharmacol119: 1081-1083. [PMID:8937708]

53. Nishi M, Houtani T, Noda Y, Mamiya T, Sato K, Doi T, Kuno J, Takeshima H, Nukada T, Nabeshima T, Yamashita T, Noda T, Sugimoto T. (1997) Unrestrained nociceptive response and disregulation of hearing ability in mice lacking the nociceptin/orphaninFQ receptor. EMBO J16: 1858-1864. [PMID:9155012]

54. Okada K, Sujaku T, Chuman Y, Nakashima R, Nose T, Costa T, Yamada Y, Yokoyama M, Nagahisa A, Shimohigashi Y. (2000) Highly potent nociceptin analog containing the Arg-Lys triple repeat. Biochem Biophys Res Commun278: 493-498. [PMID:11097863]

55. Okawa H, Nicol B, Bigoni R, Hirst RA, Calo G, Guerrini R, Rowbotham DJ, Smart D, McKnight AT, Lambert DG. (1999) Comparison of the effects of [Phe1psi(CH2-NH)Gly2]nociceptin(1-13)NH2 in rat brain, rat vas deferens and CHO cells expressing recombinant human nociceptin receptors. Br J Pharmacol127: 123-130. [PMID:10369464]

56. Ozaki S, Kawamoto H, Itoh Y, Miyaji M, Azuma T, Ichikawa D, Nambu H, Iguchi T, Iwasawa Y, Ohta H. (2000) In vitro and in vivo pharmacological characterization of J-113397, a potent and selective non-peptidyl ORL1 receptor antagonist. Eur J Pharmacol402: 45-53. [PMID:10940356]

57. Pan YX, Cheng J, Xu J, Rossi G, Jacobson E, Ryan-Moro J, Brooks AI, Dean GE, Standifer KM, Pasternak GW. (1995) Cloning and functional characterization through antisense mapping of a kappa 3-related opioid receptor. Mol Pharmacol47: 1180-1188. [PMID:7603458]

58. Reinscheid RK, Nothacker HP, Bourson A, Ardati A, Henningsen RA, Bunzow JR, Grandy DK, Langen H, Monsma FJ Jr, Civelli O. (1995) Orphanin-FQ: a neuropeptide that activates an opioid-like G protein-coupled receptor. Science270: 792-794. [PMID:7481766]

59. Rizzi A, Spagnolo B, Wainford RD, Fischetti C, Guerrini R, Marzola G, Baldisserotto A, Salvadori S, Regoli D, Kapusta DR et al.. (2007) In vitro and in vivo studies on UFP-112, a novel potent and long lasting agonist selective for the nociceptin/orphanin FQ receptor. Peptides28 (6): 1240-51. [PMID:17532097]

60. Schlicker E, Werthwein S, Kathmann M, Bauer U. (1998) Nociceptin inhibits noradrenaline release in the mouse brain cortex via presynaptic ORL1 receptors. Naunyn Schmiedebergs Arch Pharmacol358: 418-422. [PMID:9826063]

61. Shinkai H, Ito T, Iida T, Kitao Y, Yamada H, Uchida I. (2000) 4-Aminoquinolines: novel nociceptin antagonists with analgesic activity. J Med Chem43: 4667-4677. [PMID:11101358]

62. Slowe SJ, Clarke S, Lena I, Goody RJ, Lattanzi R, Negri L, Simonin F, Matthes HW, Filliol D, Kieffer BL, Kitchen I. (2001) Autoradiographic mapping of the opioid receptor-like 1 (ORL1) receptor in the brains of mu-, delta- or kappa-opioid receptor knockout mice. Neuroscience106: 469-480. [PMID:11591451]

63. Thompson AA, Liu W, Chun E, Katritch V, Wu H, Vardy E, Huang XP, Trapella C, Guerrini R, Calo G et al.. (2012) Structure of the nociceptin/orphanin FQ receptor in complex with a peptide mimetic. Nature485 (7398): 395-9. [PMID:22596163]

64. Ueda H, Inoue M, Takeshima H, Iwasawa Y. (2000) Enhanced spinal nociceptin receptor expression develops morphine tolerance and dependence. J Neurosci20: 7640-7647. [PMID:11027224]

65. Wang HL, Hsu CY, Huang PC, Kuo YL, Li AH, Yeh TH, Tso AS, Chen YL. (2005) Heterodimerization of opioid receptor-like 1 and mu-opioid receptors impairs the potency of micro receptor agonist. J Neurochem92: 1285-1294. [PMID:15748148]

66. Wang JB, Johnson PS, Imai Y, Persico AM, Ozenberger BA, Eppler CM, Uhl GR. (1994) CDNA cloning of an orphan opiate receptor gene family member and its splice variant. FEBS Lett.348: 75-79. [PMID:8026588]

67. Zaratin PF, Petrone G, Sbacchi M, Garnier M, Fossati C, Petrillo P, Ronzoni S, Giardina GA, Scheideler MA. (2004) Modification of nociception and morphine tolerance by the selective opiate receptor-like orphan receptor antagonist (-)-cis-1-methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol (SB-612111). J Pharmacol Exp Ther308: 454-461. [PMID:14593080]

68. Zaveri N. (2003) Peptide and nonpeptide ligands for the nociceptin/orphanin FQ receptor ORL1: research tools and potential therapeutic agents. Life Sci73: 663-678. [PMID:12801588]

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: NOP receptor. Last modified on 01/04/2014. Accessed on 21/10/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=320.

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