Nociceptinski receptor

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

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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]

Literatura

↑ Mollereau C, Parmentier M, Mailleux P, Butour JL, Moisand C, Chalon P, Caput D, Vassart G, Meunier JC (March 1994). „ORL1, a novel member of the opioid receptor family. Cloning, functional expression and localization”. FEBS Lett. 341 (1): 33–8. DOI:10.1016/0014-5793(94)80235-1. PMID 8137918.
↑ Henderson G, McKnight AT (August 1997). „The orphan opioid receptor and its endogenous ligand--nociceptin/orphanin FQ”. Trends Pharmacol. Sci. 18 (8): 293–300. DOI:10.1016/S0165-6147(97)90645-3. PMID 9277133.
↑ „Entrez Gene: OPRL1 opiate receptor-like 1”.
↑ Liu Z, Wang Y, Zhang J, Ding J, Guo L, Cui D, Fei J (March 2001). „Orphanin FQ: an endogenous antagonist of rat brain dopamine transporter”. Neuroreport 12 (4): 699–702. DOI:10.1097/00001756-200103260-00017. PMID 11277567.
↑ ^5,0 ^5,1 Calo' G, Guerrini R, Rizzi A, Salvadori S, Regoli D (April 2000). „Pharmacology of nociceptin and its receptor: a novel therapeutic target”. Br. J. Pharmacol. 129 (7): 1261–83. DOI:10.1038/sj.bjp.0703219. PMC 1571975. PMID 10742280.
↑ Mørk H, Hommel K, Uddman R, Edvinsson L, Jensen R (September 2002). „Does nociceptin play a role in pain disorders in man?”. Peptides 23 (9): 1581–7. DOI:10.1016/S0196-9781(02)00101-8. PMID 12217418.
↑ Scoto GM, Aricò G, Ronsisvalle S, Parenti C (July 2007). „Blockade of the nociceptin/orphanin FQ/NOP receptor system in the rat ventrolateral periaqueductal gray potentiates DAMGO analgesia”. Peptides 28 (7): 1441–6. DOI:10.1016/j.peptides.2007.05.013. PMID 17628212.
↑ Redrobe JP, Calo' G, Regoli D, Quirion R (February 2002). „Nociceptin receptor antagonists display antidepressant-like properties in the mouse forced swimming test”. Naunyn Schmiedebergs Arch. Pharmacol. 365 (2): 164–7. DOI:10.1007/s00210-001-0511-0. PMID 11819035.
↑ Khroyan TV, Polgar WE, Jiang F, Zaveri NT, Toll L (December 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. DOI:10.1124/jpet.109.156711. PMC 2784721. PMID 19713488.

Dodatna literatura

Mollereau C, Mouledous L (2000). „Tissue distribution of the opioid receptor-like (ORL1) receptor.”. Peptides 21 (7): 907–17. DOI:10.1016/S0196-9781(00)00227-8. PMID 10998524.
New DC, Wong YH (2003). „The ORL1 receptor: molecular pharmacology and signalling mechanisms.”. Neurosignals 11 (4): 197–212. DOI:10.1159/000065432. 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. DOI:10.1016/S0024-3205(03)00387-4. 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. DOI:10.1016/0169-328X(95)00096-B. 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.
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. DOI:10.1016/S0014-5793(99)01317-4. 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. DOI:10.1159/000014645. 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. DOI:10.1016/S0169-328X(02)00390-X. 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. PMC 139241. 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. DOI:10.1007/s000180200016. PMID 12568343.

Vanjske veze

„Opioid Receptors: NOP”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Arhivirano iz originala na datum 2016-03-03.
MeSH nociceptin+receptor

[pmid8137918-1] Mollereau C, Parmentier M, Mailleux P, Butour JL, Moisand C, Chalon P, Caput D, Vassart G, Meunier JC (March 1994). „ORL1, a novel member of the opioid receptor family. Cloning, functional expression and localization”. FEBS Lett. 341 (1): 33–8. DOI:10.1016/0014-5793(94)80235-1. PMID 8137918.

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

[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 (March 2001). „Orphanin FQ: an endogenous antagonist of rat brain dopamine transporter”. Neuroreport 12 (4): 699–702. DOI:10.1097/00001756-200103260-00017. PMID 11277567.

[pmid10742280-5] 5,0 ^5,1 Calo' G, Guerrini R, Rizzi A, Salvadori S, Regoli D (April 2000). „Pharmacology of nociceptin and its receptor: a novel therapeutic target”. Br. J. Pharmacol. 129 (7): 1261–83. DOI:10.1038/sj.bjp.0703219. PMC 1571975. PMID 10742280.

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

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

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

[pmid19713488-9] Khroyan TV, Polgar WE, Jiang F, Zaveri NT, Toll L (December 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. DOI:10.1124/jpet.109.156711. PMC 2784721. PMID 19713488.

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