Nociceptin receptor

Opiate receptor-like 1
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes
Identifiers
Symbols	; KOR-3; NOCIR; OOR; ORL1
External IDs	IUPHAR: ChEMBL: GeneCards:
Gene ontology Molecular function • • • Cellular component • • • Biological process • • • • • • Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

The nociceptin receptor or NOP also known as the orphanin FQ receptor or kappa-type 3 opioid receptor is a protein that in humans is encoded by the OPRL1 (opioid receptor-like 1) gene.^[1] The nociceptin receptor is a G protein-coupled receptor whose natural ligand is known as nociceptin or orphanin FQ, a 17 amino acid neuropeptide.^[2] This receptor is involved in the regulation of numerous brain activities, particularly instinctive and emotional behaviors.^[3]

Mechanism

Nociceptin is thought to be an endogenous antagonist of dopamine transport that may act either directly on dopamine or by inhibiting GABA to affect dopamine levels.^[4] Within the central nervous system its action can be either similar or opposite to those of opioids depending on their location.^[5] It controls a wide range of biological functions ranging from nociception to food intake, from memory processes to cardiovascular and renal functions, from spontaneous locomotor activity to gastrointestinal motility, from anxiety to the control of neurotransmitter release at peripheral and central sites.^[5]

Selective ligands

Several commonly used opioid drugs including etorphine and buprenorphine have been demonstrated to bind to nociceptin receptors, but this binding is relatively insignificant compared to their activity at other opioid receptors. More recently a range of selective ligands for NOP have been developed, which show little or no affinity to other opioid receptors and so allow NOP-mediated responses to be studied in isolation.

Agonists

• Buprenorphine (partial agonist, not selective for NOP, also partial agonist of µ-opioid and δ-opioid receptors, and competitive antagonist of κ-opioid receptors)
• Cebranopadol (full agonist at NOP, μ-opioid and δ-opioid receptors, partial agonist at κ-opioid receptor)
• Etorphine
• MT-7716
• Nociceptin
• Norbuprenorphine (full agonist; non-selective (also full agonist at the MOR and DOR and partial agonist at the KOR; peripherally-selective)
• NNC 63-0532
• Ro64-6198
• Ro65-6570
• SCH-221,510
• SR-8993
• SR-16435 (mixed MOR / NOP partial agonist)
• MCOPPB^[6] (full agonist, CAS# 1028969-49-4)

Antagonists

• JTC-801
• J-113,397
• SB-612,111
• SR-16430

Applications

NOP agonists are being studied as treatments for heart failure and migraine^[7] while nociceptin antagonists such as JTC-801 may have analgesic^[8] and antidepressant qualities.^[9]

References

Further reading

External links

• "Opioid Receptors: NOP". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. 
• nociceptin receptor at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Cell surface receptor: G protein-coupled receptors   Class A: Rhodopsin like Neurotransmitter Adrenergic α1 (A B D) α2 (A B C) β1 β2 β3 Purinergic Adenosine (A1 A2A A2B A3) P2Y (1 2 4 5 6 8 9 10 11 12 13 14) Serotonin (all but 5-HT3) 5-HT1 (A B D E F) 5-HT2 (A B C) 5-HT (4 5A 6 7) Other Acetylcholine (M1 M2 M3 M4 M5) Dopamine (D1 D2 D3 D4 D5) Histamine (H1 H2 H3 H4) Melatonin (1A 1B 1C) TAAR (1 2 3 5 6 8 9) Metabolites and signaling molecules Eicosanoid CysLT (1 2) LTB4 (1 2) FPRL1 OXE Prostaglandin (DP (1 2), EP (1 2 3 4), FP) Prostacyclin Thromboxane Other Bile acid Cannabinoid (CB1 CB2, GPR (18 55 119)) EBI2 Estrogen Free fatty acid (1 2 3 4) Lactate Lysophosphatidic acid (1 2 3 4 5 6) Lysophospholipid (1 2 3 4 5 6 7 8) Niacin (1 2) Oxoglutarate PAF Sphingosine-1-phosphate (1 2 3 4 5) Succinate Peptide Neuropeptide B/W (1 2) FF (1 2) S Y (1 2 4 5) Neuromedin (B U (1 2)) Neurotensin (1 2) Other Anaphylatoxin (C3a C5a) Angiotensin (1 2) Apelin Bombesin (BRS3 GRPR NMBR) Bradykinin (B1 B2) Chemokine Cholecystokinin (A B) Endothelin (A B) Formyl peptide (1 2 3) FSH Galanin (1 2 3) GHB receptor Gonadotropin-releasing hormone (1 2) Ghrelin Kisspeptin Luteinizing hormone/choriogonadotropin MAS (1 1L D E F G X1 X2 X3 X4) Melanocortin (1 2 3 4 5) MCHR (1 2) Motilin Opioid (Delta Kappa Mu Nociceptin & Zeta, but not Sigma) Orexin (1 2) Oxytocin Prokineticin (1 2) Prolactin-releasing peptide Relaxin (1 2 3 4) Somatostatin (1 2 3 4 5) Tachykinin (1 2 3) Thyrotropin Thyrotropin-releasing hormone Urotensin-II Vasopressin (1A 1B 2) Miscellaneous Orphan GPR (1 3 4 6 12 15 17 18 19 20 21 22 23 25 26 27 31 32 33 34 35 37 39 42 44 45 50 52 55 61 62 63 65 68 75 77 78 81 82 83 84 85 87 88 92 101 103 109A 109B 119 120 132 135 137B 139 141 142 146 148 149 150 151 152 153 160 161 162 171 173 174 176 177 182 183) Other Adrenomedullin Olfactory Opsin (3 4 5 1LW 1MW 1SW RGR RRH) Protease-activated (1 2 3 4) SREB (1 2 3)   Class B: Secretin like Orphan GPR (56 64 97 98 110 111 112 113 114 115 116 123 124 125 126 128 133 143 144 155 157) Other Brain-specific angiogenesis inhibitor (1 2 3) Cadherin (1 2 3) Calcitonin CALCRL CD97 Corticotropin-releasing hormone (1 2) EMR (1 2 3) Glucagon (GR GIPR GLP1R GLP2R) Growth hormone releasing hormone PACAPR1 GPR Latrophilin (1 2 3 ELTD1) Methuselah-like proteins Parathyroid hormone (1 2) Secretin Vasoactive intestinal peptide (1 2)   Class C: Metabotropic glutamate / pheromone Taste TAS1R (1 2 3) TAS2R (1 3 4 5 7 8 9 10 13 14 16 19 20 30 31 38 39 40 41 42 43 45 46 50 60) Other Calcium-sensing receptor GABA B (1 2) Glutamate receptor (Metabotropic glutamate (1 2 3 4 5 6 7 8)) GPRC6A GPR (156 158 179) RAIG (1 2 3 4)   Class F: Frizzled / Smoothened Frizzled Frizzled (1 2 3 4 5 6 7 8 9 10) Smoothened Smoothened : (///), (, , , , , //), (, , ), , ; path (, , +, , , , , )

Neuropeptide receptors G protein-coupled receptor Hormone receptors Hypothalamic CRH FSH LHRH TRH Somatostatin Pituitary Vasopressin 1A 1B 2 Oxytocin LHCG TSH Other Atrial natriuretic factor NPR3 Calcitonin Cholecystokinin A B VIP Opioid receptors Delta Kappa Mu Nociceptin Other neuropeptide receptors Angiotensin Bradykinin B1 B2 Tachykinin TACR1 Calcitonin gene-related peptide Galanin GPCR neuropeptide B/W FF S Y Neurotensin Type I cytokine receptor GH Prolactin Enzyme-linked receptor Atrial natriuretic factor NPR1 NPR2 Other Sigma 1 2 : (///), (, , , , , //), (, , ), , ; path (, , +, , , , , )

Opioidergics Receptor (ligands) MOR Agonists: 7-Hydroxymitragynine ψ-Akuammigine Acetyldihydrocodeine Acetylfentanyl Adrenorphin (metorphamide) AH-7921 Akuammidine Alfentanil Anileridine β-Endorphin Benzylmorphine Bezitramide Biphalin Buprenorphine Butorphanol Butyrfentanyl Carfentanil Casokefamide Cebranopadol Codeine DADLE Dermorphin Desomorphine Dextromoramide Dextropropoxyphene (propoxyphene) Dezocine Diamorphine (heroin) Dihydrocodeine Dihydromorphine Diphenoxylate Dipipanone Dynorphin A Endomorphin-1 Endomorphin-2 Eseroline Ethylmorphine Etorphine Fentanyl Frakefamide Hemorphin-4 Herkinorin Hodgkinsine Hydrocodone Hydromorphinol Hydromorphone IBNtxA Ketamine Ketobemidone Kratom Laudanosine Lefetamine Leu-enkephalin Levacetylmethadol Levorphanol Loperamide Meptazinol Met-enkephalin Methadone Metkefamide Metopon Mitragynine Mitragynine pseudoindoxyl Morphiceptin Morphine Nalbuphine Naltalimide Nicocodeine Nicodicodeine Nicomorphine O-Desmethyltramadol Octreotide Opium poppy (opium) Oripavine Oxycodone Oxymorphone Pentazocine Pericine Pethidine (meperidine) Phenazocine Phencyclidine Piminodine Piritramide Prodine Propiram Remifentanil Sufentanil Tapentadol Thebaine Tianeptine Tilidine Tramadol TRIMU 5 TRV130 TRV734 U-47700 Valorphin Note: The above list contains only some known MOR agonists, as too many exist to list here completely. Refer here instead for more. PAMs: BMS-986121 BMS-986122 Antagonists: (3S,4S)-Picenadol 2-(S)-N,N-(R)-Viminol 4-Caffeoyl-1,5-quinide 6β-Naltrexol-d4 18-MC Akuammine Alvimopan Chlornaltrexamine Chloroxymorphamine Cyprodime Diprenorphine Eptazocine Gemazocine Ibogaine Levallorphan Lobeline LY-255582 Methylnaltrexone Naldemedine Nalmefene Nalorphine Nalorphine dinicotinate Naloxazone Naloxegol Naloxol Naloxonazine Naloxone Naltrexone Noribogaine Oxilorphan Quadazocine Samidorphan DOR Agonists: 6'-GNTI 7-SIOM ADL-5859 β-Endorphin Biphalin BU-48 Butorphanol BW373U86 Casokefamide Cebranopadol Codeine Cyclazocine DADLE Deltorphin A Deltorphin I Deltorphin II Desmethylclozapine Dezocine Diamorphine (heroin) Dihydromorphine DPDPE DPI-221 DPI-3290 Ethylketazocine Etorphine Fentanyl Hemorphin-4 Hydrocodone Hydromorphone Ibogaine Isomethadone Kratom Laudanosine Leu-enkephalin Lofentanil Met-enkephalin Metazocine Metkefamide Mitragynine Mitragynine pseudoindoxyl Morphine N-Phenethyl-14-ethoxymetopon Nalbuphine Norbuprenorphine O-Desmethyltramadol Oxycodone Oxymorphone Pethidine (meperidine) Proglumide RWJ-394674 SKF-10047 SNC-80 TAN-67 (SB-205,607) Thebaine Thiobromadol (C-8813) Tianeptine Tonazocine Tramadol Xorphanol Zenazocine Antagonists: 6β-Naltrexol-d4 Amentoflavone Diprenorphine ICI-174864 LY-255582 Methylnaltrexone Nalmefene Nalorphine Naltrexone Naltriben Naltrindole Naloxone Noribogaine Quadazocine SoRI-9409 KOR Agonists: 6'-GNTI 8-CAC 18-MC 14-Methoxymetopon Adrenorphin (metorphamide) Alazocine Asimadoline Big dynorphin Bremazocine BRL-52537 Butorphanol Cebranopadol Ciprefadol CR845 Cyclazocine Cyclorphan Cyprenorphine Diamorphine (heroin) Dihydromorphine Dynorphin A Dynorphin B Enadoline Eptazocine Ethylketazocine Etorphine FE 200665 (CR665) Fedotozine Fentanyl Gemazocine GR-89696 Hemorphin-4 Herkinorin Hydromorphone HZ-2 Ibogaine ICI-199,441 ICI-204,448 Ketamine Ketazocine Leumorphin (dynorphin B-29) Levallorphan Levorphanol Lofentanil LPK-26 Lufuradom Matrine Menthol Metazocine Metkefamide Morphine Moxazocine N-MPPP Nalbuphine Nalfurafine Nalorphine Naltriben Norbuprenorphine Norbuprenorphine-3-glucuronide O-Desmethyltramadol Oxilorphan Oxycodone Pentazocine Pethidine (meperidine) Phenazocine Proxorphan RB-64 Salvinorin A (salvia) Salvinorin B ethoxymethyl ether Salvinorin B methoxymethyl ether SKF-10047 Spiradoline (U-62,066) Tifluadom U-50,488 U-54,494A U-69,593 Xorphanol Antagonists: 5'-GNTI 6β-Naltrexol-d4 ALKS-5461 Amentoflavone ANTI Binaltorphimine BU09059 Buprenorphine Dezocine DIPPA Diprenorphine JDTic LY-255582 LY-2456302 LY-2459989 LY-2795050 Methylnaltrexone ML190 ML350 MR-2266 Nalmefene Naloxone Naltrexone Norbinaltorphimine Noribogaine Pawhuskin A PF-4455242 Quadazocine Zyklophin NOP Agonists: Buprenorphine Cebranopadol Etorphine MCOPPB MT-7716 NNC 63-0532 Nociceptin (orphanin FQ) Norbuprenorphine Ro64-6198 Ro65-6570 SCH-221,510 SR-8993 SR-16435 Antagonists: J-113,397 JTC-801 SB-612,111 SR-16430 Unsorted / unknown β-Casomorphins Amidorphin Cannabidiol Coronaridine Cyproterone acetate Cytochrophin-4 Deprolorphin Diacetylnalorphine Difenamizole Fluorophen Gliadorphin (gluteomorphin) Gluten exorphins Hemorphins Ibogamine Nalmexone Neoendorphins Rubiscolins Soymorphins Tabernanthine THC Enzyme (inhibitors) Enkephalinase BL-2401 Candoxatril D-Phenylalanine Ecadotril Kelatorphan Racecadotril (acetorphan) RB-101 RB-120 RB-3007 Selank Semax Spinorphin Thiorphan Tynorphin Ubenimex (bestatin)