title: Cellular mechanisms of nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor regulation and heterologous regulation by N/OFQ.
abstract: The nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor is the fourth and most recently discovered member of the opioid receptor superfamily that also includes μ, δ, and κ opioid receptor subtypes (MOR, DOR, and KOR, respectively). The widespread anatomic distribution of the NOP receptor enables the modulation of several physiologic processes by its endogenous agonist, N/OFQ. Accordingly, the NOP receptor has gained a lot of attention as a potential target for the development of ligands with therapeutic use in several pathophysiological states. NOP receptor activation frequently results in effects opposing classic opioid receptor action; therefore, regulation of the NOP receptor and conditions affecting its modulatory tone are important to understand. Mounting evidence reveals a heterologous interaction of the NOP receptor with other G protein-coupled receptors, including MOR, DOR, and KOR, which may subsequently influence their function. Our focus in this review is to summarize and discuss the findings that delineate the cellular mechanisms of NOP receptor signaling and regulation and the regulation of other receptors by N/OFQ and the NOP receptor.
authors: Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, USA.
authors: Courtney L
authors: CL
authors: Donica
authors: Hibah O
authors: HO
authors: Awwad
authors: Deepak R
authors: DR
authors: Thakker
authors: Kelly M
authors: KM
authors: Standifer
mesh_terms: D000818:Animals; D006801:Humans; D008024:Ligands; D018847:Opioid Peptides / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism*; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D008024:Ligands; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722283:OPRL1 protein, human
references: Life Sci. 2005 Nov 4;77(25):3127-32
references: 15985270
references: Neurosci Lett. 1997 Feb 14;223(1):49-52
references: 9058420
references: J Biol Chem. 2010 Jan 8;285(2):1032-40
references: 19887453
references: J Pharmacol Exp Ther. 1998 May;285(2):902-7
references: 9580642
references: Eur J Pharmacol. 1996 Dec 12;317(1):9-13
references: 8982713
references: J Neuroimmunol. 1998 Jan;81(1-2):184-92
references: 9521621
references: Br J Pharmacol. 2006 Feb;147(4):391-401
references: 16402042
references: Eur J Pharmacol. 1998 Jun 19;351(2):247-52
references: 9687009
references: J Comp Neurol. 1999 Oct 4;412(4):563-605
references: 10464356
references: Mol Pharmacol. 1995 Jun;47(6):1180-8
references: 7603458
references: Neuroreport. 1998 Mar 9;9(4):631-6
references: 9559929
references: Nat Neurosci. 2004 Feb;7(2):118-25
references: 14730309
references: J Neurosci. 1996 Nov 1;16(21):6657-64
references: 8824306
references: J Immunol. 2001 Mar 15;166(6):3650-4
references: 11238602
references: Neuroreport. 1998 Aug 24;9(12):2703-8
references: 9760105
references: Exp Cell Res. 1999 Feb 25;247(1):233-40
references: 10047465
references: Neuroscience. 2009 Sep 29;163(1):308-15
references: 19527777
references: Nature. 1989 Jul 6;340(6228):35-41
references: 2739723
references: FEBS Lett. 1997 Jul 28;412(2):290-4
references: 9256237
references: FEBS Lett. 1994 Jul 4;348(1):75-9
references: 8026588
references: J Physiol. 2001 Aug 1;534(Pt 3):849-59
references: 11483714
references: J Pharmacol Exp Ther. 2002 Aug;302(2):502-9
references: 12130708
references: J Neuroimmunol. 2004 Apr;149(1-2):110-20
references: 15020071
references: Br J Pharmacol. 2003 Sep;140(1):61-70
references: 12967935
references: Physiol Behav. 1996 Jan;59(1):123-32
references: 8848471
references: Naunyn Schmiedebergs Arch Pharmacol. 2007 Nov;376(3):217-25
references: 17899014
references: Nature. 1995 Oct 12;377(6549):532-5
references: 7566152
references: Brain Res. 1999 Aug 14;838(1-2):85-94
references: 10446320
references: Brain Res Mol Brain Res. 1995 Sep;32(2):342-7
references: 7500847
references: J Neuroimmunol. 2002 Sep;130(1-2):100-8
references: 12225892
references: Nat Med. 2010 Nov;16(11):1267-76
references: 20948535
references: Neurosignals. 2002 Mar-Apr;11(2):115-22
references: 12077485
references: FEBS Lett. 1994 Apr 18;343(1):42-6
references: 8163014
references: Cell Mol Life Sci. 2002 Dec;59(12):2172-83
references: 12568343
references: J Neurochem. 1998 Nov;71(5):2186-92
references: 9798946
references: Br J Pharmacol. 1996 Dec;119(8):1614-8
references: 8982509
references: Curr Opin Pharmacol. 2012 Feb;12(1):55-61
references: 22019566
references: Biochem Biophys Res Commun. 2002 Sep 27;297(3):659-63
references: 12270145
references: Mol Cell Biol. 1992 Jul;12(7):3149-54
references: 1620122
references: Peptides. 1996;17(5):763-8
references: 8844764
references: J Neuroimmune Pharmacol. 2010 Mar;5(1):143-54
references: 20119853
references: Biochemistry. 2003 Sep 9;42(35):10498-505
references: 12950177
references: Neurosci Lett. 1996 Aug 23;214(2-3):131-4
references: 8878101
references: J Peripher Nerv Syst. 2006 Sep;11(3):232-40
references: 16930285
references: Brain Res. 1994 Sep 19;657(1-2):133-40
references: 7820610
references: J Biol Chem. 2012 Dec 7;287(50):42019-30
references: 23086955
references: J Neurosci. 2000 Oct 15;20(20):7640-7
references: 11027224
references: Pharmacol Rev. 2001 Sep;53(3):381-415
references: 11546835
references: Br J Pharmacol. 2002 Aug;136(7):1065-71
references: 12145107
references: Eur J Pharmacol. 1996 Sep 5;311(1):R3-5
references: 8884244
references: Neuroscience. 2007 Jan 5;144(1):275-85
references: 17069983
references: Peptides. 2000 Jul;21(7):907-17
references: 10998524
references: Eur J Pharmacol. 2002 Aug 2;449(1-2):17-22
references: 12163101
references: FEBS Lett. 1998 Sep 11;435(1):65-8
references: 9755860
references: Br J Pharmacol. 1996 May;118(2):205-7
references: 8735615
references: Neuroscience. 1997 Nov;81(1):249-54
references: 9300417
references: Jpn J Pharmacol. 1991 Jul;56(3):287-96
references: 1895575
references: J Physiol. 2012 Apr 1;590(7):1655-67
references: 22371475
references: Eur J Neurosci. 1997 Jan;9(1):194-7
references: 9042583
references: Neuropharmacology. 2012 Sep;63(3):427-33
references: 22575074
references: J Neurosci. 1997 Feb 1;17(3):996-1003
references: 8994054
references: J Pharmacol Exp Ther. 2001 Aug;298(2):812-9
references: 11454946
references: Annu Rev Pharmacol Toxicol. 1998;38:289-319
references: 9597157
references: J Pharmacol Exp Ther. 2003 Sep;306(3):965-72
references: 12750434
references: Eur J Neurosci. 1999 Oct;11(10):3610-6
references: 10564368
references: Neuroreport. 2006 Feb 6;17(2):173-7
references: 16407766
references: Pain. 2004 Jul;110(1-2):236-45
references: 15275773
references: Cell. 2009 Oct 16;139(2):267-84
references: 19837031
references: Mol Pharmacol. 2005 Aug;68(2):447-56
references: 15890842
references: Genes Cells. 2012 Apr;17(4):249-63
references: 22380515
references: Trends Pharmacol Sci. 2002 Sep;23(9):403-4
references: 12237149
references: Addict Biol. 2008 Jun;13(2):147-59
references: 18482430
references: Br J Pharmacol. 1998 Oct;125(3):510-6
references: 9806334
references: Acupunct Electrother Res. 1996 Jul-Dec;21(3-4):199-205
references: 9051167
references: FEBS Lett. 1994 Jun 27;347(2-3):284-8
references: 8034019
references: Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14854-8
references: 9405703
references: FEBS Lett. 1997 Feb 10;403(1):91-4
references: 9038367
references: Clin Neuropharmacol. 1995 Aug;18(4):285-305
references: 8665542
references: Brain Res Mol Brain Res. 1994 Nov;27(1):37-44
references: 7877452
references: FEBS Lett. 1994 Jun 27;347(2-3):279-83
references: 8034018
references: Life Sci. 1999;64(22):2029-37
references: 10374928
references: J Neuroimmune Pharmacol. 2011 Dec;6(4):617-25
references: 21547539
references: Neurochem Res. 1996 Nov;21(11):1387-96
references: 8947929
references: Brain Res. 1999 May 15;828(1-2):74-82
references: 10320726
references: Br J Pharmacol. 1999 May;127(1):123-30
references: 10369464
references: Brain Res. 2000 Jul 21;871(2):192-200
references: 10899286
references: Cell Signal. 2006 May;18(5):670-8
references: 16019191
references: J Mol Neurosci. 2012 Feb;46(2):285-92
references: 21603976
references: Nat Neurosci. 2006 Jan;9(1):31-40
references: 16311589
references: Science. 1995 Nov 3;270(5237):792-4
references: 7481766
references: Life Sci. 1997;60(1):PL15-21
references: 8995537
references: Results Probl Cell Differ. 2008;46:1-25
references: 18193175
references: Trends Pharmacol Sci. 1997 Dec;18(12):456-64
references: 9458693
references: Neuroscience. 2001;106(3):469-80
references: 11591451
references: Br J Pharmacol. 1996 Apr;117(8):1609-11
references: 8732266
references: J Mol Neurosci. 2005;25(1):21-7
references: 15781963
references: Science. 1997 Oct 3;278(5335):58-63
references: 9311927
references: Brain Res. 2005 May 10;1043(1-2):214-7
references: 15862535
references: Trends Neurosci. 1995 Jan;18(1):22-9
references: 7535487
references: Brain Res Mol Brain Res. 2002 Sep 30;105(1-2):38-46
references: 12399106
references: Eur J Pharmacol. 2000 Aug 18;402(1-2):R1-37
references: 10940375
references: Neuropeptides. 2011 Aug;45(4):247-61
references: 21477860
references: Biochem Biophys Res Commun. 2003 Apr 11;303(3):920-5
references: 12670499
references: Neuroreport. 1997 May 27;8(8):1913-8
references: 9223076
references: Neurosci Lett. 1996 Feb 2;204(1-2):29-32
references: 8929970
references: Hippocampus. 1997;7(1):88-94
references: 9138672
references: Biochem Biophys Res Commun. 1997 Nov 17;240(2):304-8
references: 9388473
references: Neuropharmacology. 2002 Nov;43(6):979-90
references: 12423667
references: Annu Rev Neurosci. 2004;27:107-44
references: 15217328
references: Br J Pharmacol. 2003 May;139(2):362-7
references: 12770941
references: J Immunol. 1997 Dec 1;159(11):5273-84
references: 9548466
references: Neuroscience. 2003;117(1):157-68
references: 12605902
references: J Physiol. 1998 May 15;509 ( Pt 1):47-58
references: 9547380
references: J Immunol. 1999 Apr 1;162(7):3819-29
references: 10201899
references: J Neuroimmunol. 1995 Jun;59(1-2):91-101
references: 7797625
references: Endocrinology. 2004 Jun;145(6):2876-85
references: 15016723
references: Neuroscience. 2003;121(3):629-40
references: 14568023
references: Peptides. 2007 Nov;28(11):2243-52
references: 17950489
references: Neuroendocrinology. 1998 Feb;67(2):73-82
references: 9508037
references: FEBS Lett. 1997 Jul 21;412(1):253-6
references: 9257731
references: J Physiol. 2001 Oct 1;536(Pt 1):35-47
references: 11579155
references: Can J Physiol Pharmacol. 1998 Mar;76(3):314-24
references: 9673795
references: Naunyn Schmiedebergs Arch Pharmacol. 2001 May;363(5):551-5
references: 11383716
references: Neuroreport. 2001 Oct 8;12(14):3159-63
references: 11568656
references: J Neurochem. 1998 Sep;71(3):1024-33
references: 9721727
references: Neuroreport. 1996 Dec 20;8(1):369-71
references: 9051812
references: Pain. 2010 Mar;148(3):414-425
references: 20036056
references: Neuroreport. 1999 Jan 18;10(1):103-6
references: 10094142
references: Brain Res Bull. 2001 Apr;54(6):655-60
references: 11403992
references: J Neuroimmune Pharmacol. 2011 Dec;6(4):546-50
references: 21656184
references: J Neurochem. 1998 Nov;71(5):2203-10
references: 9798948
references: J Pharmacol Exp Ther. 2000 Dec;295(3):1094-100
references: 11082445
references: J Pharmacol Exp Ther. 2004 Nov;311(2):645-51
references: 15254141
references: J Pharmacol Exp Ther. 1998 Jul;286(1):136-41
references: 9655852
references: FEBS Lett. 1994 Mar 14;341(1):33-8
references: 8137918
references: J Neurochem. 2005 Mar;92(6):1285-94
references: 15748148