Nociceptinski receptor

Opijatnom receptoru sličan 1
Opijatnom receptoru sličan 1
Identifikatori
Simboli	OPRL1; KOR-3; MGC34578; NOCIR; OOR; ORL1
Vanjski ID	OMIM: 602548 MGI: 97440 HomoloGene: 22609 IUPHAR: NOP GeneCards: OPRL1 Gene
Ontologija gena
Molekularna funkcija	• aktivnost rodopsinu sličnog receptora; • receptorska aktivnost; • aktivnost X-opioidnog receptora;
Celularna komponenta	• integralno sa ćelijskom membranom; • membrana; • integralno sa membranom;
Biološki proces	• prenos signala; • signalni put G-protein spregnutog receptora; • G-proteinska signalizacija, inhibicioni put adenilat ciklaze; • elevacija koncentracije citosolnih jona kalcijuma; • sensorna percepcija;
Ortolozi
Vrsta	Čovek
Entrez	4987
Ensembl	ENSG00000125510
UniProt	P41146
RefSeq (mRNA)	XM_001131314
RefSeq (protein)	XP_001131314
Lokacija (UCSC)	Chr 20:; 62.71 - 62.74 Mb
PubMed pretraga	[1]

Nociceptinski receptor (NOP, orfaninski FQ receptor, kapa tip 3 opioidni receptor) je protein koji je kod čoveka kodiran OPRL1 (opioidnom receptoru sličan 1) genom.^[1] Nociceptinski receptor je G protein-spregnuti receptor čiji prirodni ligand je poznat kao nociceptin ili orfanin FQ, koji je neuropeptid sa 17 aminokiselina.^[2] Ovaj receptor učestvuje u regulaciji brojnih moždanih aktivnosti, posebno instinktivno i emociono ponašanje.^[3]

Mehanizam

Za nociceptin se smatra da je endogeni antagonist dopaminskog transporta. On može da deluje bilo direktno na dopamin ili putem GABA inhibicije na nivo dopamina.^[4] Unutar centralnog nervnog sistema njegovo dejstvo može da bude bilo slično ili suprotno dejstvu opioida u zavisnosti od njegove lokacije.^[5] On kontroliše širok opseg bioloških funkcija od nocicepcije do unosa hrane, od obrade memorije do kardiovaskularnih i renalnih funkcija, od spontane lokomotorne aktivnosti do gastrointestinalne motilnosti, od anksioznosti do kontrole oslobađanja neurotransmitera na perifernim i centralnim lokacijama.^[5]

Selektivni ligandi

Za nekoliko često korištenih lekova, kao što su etorfin i buprenorfin, je pokazano da se vezuju za nociceptinski receptor, ali da je to vezivanje relativno zanemarljivo u poređenju sa njihovom aktivnošću na drugim opioidnim receptorima. Nedavno je je opseg selektivnih ORL-1 liganda bio razvijen. Oni imaju mali ili nemaju afinitet za druge opioidne receptore, tako da omogućavaju studiranje ORL-1 posredovanih responsa.

Agonisti

Buprenorfin (nije selektivan za ORL-1, parcijalni agonist µ-opioidnog i δ-opioidnog receptora, i kompetitivni antagonist ϰ-opioidnog receptora)
Nociceptin
Norbuprenorfin (nije selektivan za ORL-1, takođe je pun agonist μ-opioidnog i δ-opioidnog receptora)
NNC 63-0532
Ro64-6198
Ro65-6570
SCH-221,510
SR-16435 (mešoviti mu / nociceptinski parcijalni agonist)

Antagonisti

Primene

ORL 1 agonisti se studiraju kao tretman za srčanu insuficijenciju i migrenu^[6], dok nociceptinski antagonisti, kao što je JTC-801, možda mogu da nađu primenu kao analgetici^[7] i antidepresivi.^[8]

Lek buprenorfin je parcijalni agonist ORL 1 receptora, dok je njegov metabolit norbuprenorfin pun agonist ovog receptora.^[9]

Reference

^ 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 Lett. 341 (1): 33—8. PMID 8137918. doi:10.1016/0014-5793(94)80235-1.
^ Henderson G, McKnight AT (1997). „The orphan opioid receptor and its endogenous ligand--nociceptin/orphanin FQ”. Trends Pharmacol. Sci. 18 (8): 293—300. PMID 9277133. doi:10.1016/S0165-6147(97)90645-3.
^ „Entrez Gene: OPRL1 opiate receptor-like 1”.
^ Liu Z, Wang Y, Zhang J, Ding J, Guo L, Cui D, Fei J (2001). „Orphanin FQ: an endogenous antagonist of rat brain dopamine transporter”. Neuroreport. 12 (4): 699—702. PMID 11277567. doi:10.1097/00001756-200103260-00017.
^ ^а ^б Calo' G, Guerrini R, Rizzi A, Salvadori S, Regoli D (2000). „Pharmacology of nociceptin and its receptor: a novel therapeutic target”. Br. J. Pharmacol. 129 (7): 1261—83. PMC 1571975 . PMID 10742280. doi:10.1038/sj.bjp.0703219.
^ Mørk H, Hommel K, Uddman R, Edvinsson L, Jensen R (2002). „Does nociceptin play a role in pain disorders in man?”. Peptides. 23 (9): 1581—7. PMID 12217418. doi:10.1016/S0196-9781(02)00101-8.
^ Scoto GM, Aricò G, Ronsisvalle S, Parenti C (2007). „Blockade of the nociceptin/orphanin FQ/NOP receptor system in the rat ventrolateral periaqueductal gray potentiates DAMGO analgesia”. Peptides. 28 (7): 1441—6. PMID 17628212. doi:10.1016/j.peptides.2007.05.013.
^ Redrobe JP, Calo' G, Regoli D, Quirion R (2002). „Nociceptin receptor antagonists display antidepressant-like properties in the mouse forced swimming test”. Naunyn Schmiedebergs Arch. Pharmacol. 365 (2): 164—7. PMID 11819035. doi:10.1007/s00210-001-0511-0.
^ Khroyan TV, Polgar WE, Jiang F, Zaveri NT, Toll L (2009). „Nociceptin/orphanin FQ receptor activation attenuates antinociception induced by mixed nociceptin/orphanin FQ/mu-opioid receptor agonists”. J. Pharmacol. Exp. Ther. 331 (3): 946—53. PMC 2784721 . PMID 19713488. doi:10.1124/jpet.109.156711.

Dodatna literatura

Mollereau C, Mouledous L (2000). „Tissue distribution of the opioid receptor-like (ORL1) receptor.”. Peptides. 21 (7): 907—17. PMID 10998524. doi:10.1016/S0196-9781(00)00227-8.
New DC, Wong YH (2003). „The ORL1 receptor: molecular pharmacology and signalling mechanisms.”. Neurosignals. 11 (4): 197—212. PMID 12393946. doi:10.1159/000065432.
N, Zaveri (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. doi:10.1016/S0024-3205(03)00387-4.
MJ, Wick; SR, Minnerath; S, Roy; 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. doi:10.1016/0169-328X(95)00096-B.
JC, Meunier; C, Mollereau; L, Toll; et al. (1995). „Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor.”. Nature. 377 (6549): 532—5. PMID 7566152. doi:10.1038/377532a0.
LY, Yung; SA, Joshi; RY, Chan; 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.
JA, Feild; JJ, Foley; TT, Testa; 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. doi:10.1016/S0014-5793(99)01317-4.
L, Mouledous; CM, Topham; C, Moisand; 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. doi:10.1159/000014645.
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. PMID 11090272. doi:10.1006/jmbi.2000.4212.
K, Okada; T, Sujaku; Y, Chuman; et al. (2001). „Highly potent nociceptin analog containing the Arg-Lys triple repeat.”. Biochem. Biophys. Res. Commun. 278 (2): 493—8. PMID 11097863. doi:10.1006/bbrc.2000.3822.
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.
P, Deloukas; LH, Matthews; J, Ashurst; et al. (2002). „The DNA sequence and comparative analysis of human chromosome 20.”. Nature. 414 (6866): 865—71. PMID 11780052. doi:10.1038/414865a.
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. PMID 12130708. doi:10.1124/jpet.102.033159.
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. doi:10.1016/S0169-328X(02)00390-X.
RL, Strausberg; EA, Feingold; LH, Grouse; 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. PMC 139241 . PMID 12477932. doi:10.1073/pnas.242603899.
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. doi:10.1007/s000180200016.

Spoljašnje veze

„Opioid Receptors: NOP”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Архивирано из оригинала 03. 03. 2016. г.
nociceptin+receptor на US National Library of Medicine Medical Subject Headings (MeSH)

[pmid8137918-1] 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 Lett. 341 (1): 33—8. PMID 8137918. doi:10.1016/0014-5793(94)80235-1.

[pmid9277133-2] Henderson G, McKnight AT (1997). „The orphan opioid receptor and its endogenous ligand--nociceptin/orphanin FQ”. Trends Pharmacol. Sci. 18 (8): 293—300. PMID 9277133. doi:10.1016/S0165-6147(97)90645-3.

[entrez-3] „Entrez Gene: OPRL1 opiate receptor-like 1”.

[pmid11277567-4] Liu Z, Wang Y, Zhang J, Ding J, Guo L, Cui D, Fei J (2001). „Orphanin FQ: an endogenous antagonist of rat brain dopamine transporter”. Neuroreport. 12 (4): 699—702. PMID 11277567. doi:10.1097/00001756-200103260-00017.

[pmid10742280-5] а ^б Calo' G, Guerrini R, Rizzi A, Salvadori S, Regoli D (2000). „Pharmacology of nociceptin and its receptor: a novel therapeutic target”. Br. J. Pharmacol. 129 (7): 1261—83. PMC 1571975 . PMID 10742280. doi:10.1038/sj.bjp.0703219.

[pmid12217418-6] Mørk H, Hommel K, Uddman R, Edvinsson L, Jensen R (2002). „Does nociceptin play a role in pain disorders in man?”. Peptides. 23 (9): 1581—7. PMID 12217418. doi:10.1016/S0196-9781(02)00101-8.

[pmid17628212-7] Scoto GM, Aricò G, Ronsisvalle S, Parenti C (2007). „Blockade of the nociceptin/orphanin FQ/NOP receptor system in the rat ventrolateral periaqueductal gray potentiates DAMGO analgesia”. Peptides. 28 (7): 1441—6. PMID 17628212. doi:10.1016/j.peptides.2007.05.013.

[pmid11819035-8] Redrobe JP, Calo' G, Regoli D, Quirion R (2002). „Nociceptin receptor antagonists display antidepressant-like properties in the mouse forced swimming test”. Naunyn Schmiedebergs Arch. Pharmacol. 365 (2): 164—7. PMID 11819035. doi:10.1007/s00210-001-0511-0.

[pmid19713488-9] Khroyan TV, Polgar WE, Jiang F, Zaveri NT, Toll L (2009). „Nociceptin/orphanin FQ receptor activation attenuates antinociception induced by mixed nociceptin/orphanin FQ/mu-opioid receptor agonists”. J. Pharmacol. Exp. Ther. 331 (3): 946—53. PMC 2784721 . PMID 19713488. doi:10.1124/jpet.109.156711.

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