Nociceptin receptor

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Opiate receptor-like 1
Identifiers
Symbol(s) OPRL1; KOR-3; MGC34578; NOCIR; OOR; ORL1
External IDs OMIM: 602548 MGI97440 Homologene22609
Orthologs
Human Mouse
Entrez 4987 18389
Ensembl na ENSMUSG00000027584
Uniprot na Q542U1
Refseq XM_001131314 (mRNA)
XP_001131314 (protein)
NM_011012 (mRNA)
NP_035142 (protein)
Location na Chr 2: 181.64 - 181.65 Mb
Pubmed search [1] [2]

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Nociceptin receptor

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]


An additional opioid receptor has been identified and cloned based on homology with the cDNA. This receptor is known as the nociceptin receptor or ORL 1 receptor. Its natural ligand is known alternately as nociceptin or orphanin FQ.[1]

The protein encoded by this gene is a G protein-coupled receptor whose expression can be induced by phytohemagglutinin. The encoded integral membrane protein is a receptor for the 17 aa neuropeptide nociceptin/orphanin FQ. This gene may be involved in the regulation of numerous brain activities, particularly instinctive and emotional behaviors. A promoter for this gene also functions as a promoter for another gene, regulator of G-protein signalling 19 (RGS19), located on the opposite strand. Two transcript variants encoding the same protein have been found for this gene.[2]

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.[3] Within the central nervous system its action can be either similar or opposite to those of opioids depending on their location.[4] 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]

Applications

ORL 1 agonists are being studied as treatments for heart failure and migraine[6] while nociceptin antagonists may have antidepressant qualities.[7]

The novel drug buprenorphine is a partial agonist at ORL 1 receptors while its metabolite norbuprenorphine is a full agonist at these receptors.[8]

References

  1. Henderson G, McKnight A (1997). "The orphan opioid receptor and its endogenous ligand--nociceptin/orphanin FQ". Trends Pharmacol Sci 18 (8): 293-300. PMID 9277133.
  2. Entrez Gene: OPRL1 opiate receptor-like 1.
  3. Nociceptin / Orphanin and dopamine. Retrieved on 2007-08-22.
  4. Nociceptin ( Orphanin ). Retrieved on 2007-08-22.
  5. Nociceptin ( Orphanin ). Retrieved on 2007-08-22.
  6. Nociceptin:ORL-1 as a target for analgesia. Retrieved on 2007-08-22.
  7. Nociceptin antagonists as antidepressants. Retrieved on 2007-08-22.
  8. Psychoactive Drug Mechanisms -- Neurotransmitter.net. Retrieved on 2007-08-22.

Further reading

  • Mollereau C, Mouledous L (2000). "Tissue distribution of the opioid receptor-like (ORL1) receptor.". Peptides 21 (7): 907-17. PMID 10998524.
  • New DC, Wong YH (2003). "The ORL1 receptor: molecular pharmacology and signalling mechanisms.". Neurosignals 11 (4): 197-212. PMID 12393946.
  • Zaveri N (2003). "Peptide and nonpeptide ligands for the nociceptin/orphanin FQ receptor ORL1: research tools and potential therapeutic agents.". Life Sci. 73 (6): 663-78. PMID 12801588.
  • Wick MJ, Minnerath SR, Roy S, et al. (1996). "Expression of alternate forms of brain opioid 'orphan' receptor mRNA in activated human peripheral blood lymphocytes and lymphocytic cell lines.". Brain Res. Mol. Brain Res. 32 (2): 342-7. PMID 7500847.
  • Meunier JC, Mollereau C, Toll L, et al. (1995). "Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor.". Nature 377 (6549): 532-5. doi:10.1038/377532a0. PMID 7566152.
  • Mollereau C, Parmentier M, Mailleux P, et al. (1994). "ORL1, a novel member of the opioid receptor family. Cloning, functional expression and localization.". FEBS Lett. 341 (1): 33-8. PMID 8137918.
  • Yung LY, Joshi SA, Chan RY, et al. (1999). "GalphaL1 (Galpha14) couples the opioid receptor-like1 receptor to stimulation of phospholipase C.". J. Pharmacol. Exp. Ther. 288 (1): 232-8. PMID 9862775.
  • Feild JA, Foley JJ, Testa TT, et al. (1999). "Cloning and characterization of a rabbit ortholog of human Galpha16 and mouse G(alpha)15.". FEBS Lett. 460 (1): 53-6. PMID 10571060.
  • Mouledous L, Topham CM, Moisand C, et al. (2000). "Functional inactivation of the nociceptin receptor by alanine substitution of glutamine 286 at the C terminus of transmembrane segment VI: evidence from a site-directed mutagenesis study of the ORL1 receptor transmembrane-binding domain.". Mol. Pharmacol. 57 (3): 495-502. PMID 10692489.
  • Yung LY, Tsim KW, Pei G, Wong YH (2000). "Immunoglobulin G1 Fc fragment-tagged human opioid receptor-like receptor retains the ability to inhibit cAMP accumulation.". Biological signals and receptors 9 (5): 240-7. PMID 10965058.
  • Ito E, Xie G, Maruyama K, Palmer PP (2000). "A core-promoter region functions bi-directionally for human opioid-receptor-like gene ORL1 and its 5'-adjacent gene GAIP.". J. Mol. Biol. 304 (3): 259-70. doi:10.1006/jmbi.2000.4212. PMID 11090272.
  • Okada K, Sujaku T, Chuman Y, et al. (2001). "Highly potent nociceptin analog containing the Arg-Lys triple repeat.". Biochem. Biophys. Res. Commun. 278 (2): 493-8. doi:10.1006/bbrc.2000.3822. PMID 11097863.
  • Serhan CN, Fierro IM, Chiang N, Pouliot M (2001). "Cutting edge: nociceptin stimulates neutrophil chemotaxis and recruitment: inhibition by aspirin-triggered-15-epi-lipoxin A4.". J. Immunol. 166 (6): 3650-4. PMID 11238602.
  • Deloukas P, Matthews LH, Ashurst J, et al. (2002). "The DNA sequence and comparative analysis of human chromosome 20.". Nature 414 (6866): 865-71. doi:10.1038/414865a. PMID 11780052.
  • Mandyam CD, Thakker DR, Christensen JL, Standifer KM (2002). "Orphanin FQ/nociceptin-mediated desensitization of opioid receptor-like 1 receptor and mu opioid receptors involves protein kinase C: a molecular mechanism for heterologous cross-talk.". J. Pharmacol. Exp. Ther. 302 (2): 502-9. doi:10.1124/jpet.102.033159. PMID 12130708.
  • Thakker DR, Standifer KM (2003). "Orphanin FQ/nociceptin blocks chronic morphine-induced tyrosine hydroxylase upregulation.". Brain Res. Mol. Brain Res. 105 (1-2): 38-46. PMID 12399106.
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899-903. doi:10.1073/pnas.242603899. PMID 12477932.
  • Spampinato S, Di Toro R, Alessandri M, Murari G (2003). "Agonist-induced internalization and desensitization of the human nociceptin receptor expressed in CHO cells.". Cell. Mol. Life Sci. 59 (12): 2172-83. PMID 12568343.

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


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