OX1 receptor

Target id: 321

Nomenclature: OX1 receptor

Family: Orexin receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for OX1 receptor in GtoImmuPdb

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 425 1p35.2 HCRTR1 hypocretin receptor 1 68
Mouse 7 416 4q- D2.2 Hcrtr1 hypocretin (orexin) receptor 1 16,68
Rat 7 416 5q36 Hcrtr1 hypocretin receptor 1 68
Previous and Unofficial Names
OX1R
Hctr1
hypocretin receptor 1
orexin receptor type 1
hypocretin (orexin) receptor 1
Database Links
Specialist databases
GPCRDB ox1r_human (Hs), ox1r_rat (Rn)
Other databases
ChEMBL Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Structures of the human OX1 orexin receptor bound to selective and dual antagonists.
PDB Id:  4ZJC
Ligand:  SB-674042
Resolution:  2.83Å
Species:  Human
References:  81
Image of receptor 3D structure from RCSB PDB
Description:  Structures of the human OX1 orexin receptor bound to selective and dual antagonists.
PDB Id:  4ZJ8
Ligand:  suvorexant
Resolution:  2.75Å
Species:  Human
References:  81
Natural/Endogenous Ligands
orexin-A {Sp: Human, Mouse, Rat}
orexin-B {Sp: Human} , orexin-B {Sp: Mouse, Rat}
Potency order of endogenous ligands
orexin-A (HCRT, O43612) > orexin-B (HCRT, O43612)

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
orexin-A {Sp: Human, Mouse, Rat} Hs Full agonist 6.5 – 10.2 pEC50 2,18,29-31,33-36,41,46,60,68,70,72,74-75
pEC50 6.5 – 10.2 [2,18,29-31,33-36,41,46,60,68,70,72,74-75]
orexin-B {Sp: Human} Hs Full agonist 5.8 – 9.2 pEC50 2,30-31,34-35,46,60,63,68,70,72,74
pEC50 5.8 – 9.2 [2,30-31,34-35,46,60,63,68,70,72,74]
[Ala11, D-Leu15]orexin-B Hs Full agonist 6.1 – 7.3 pEC50 5,63
pEC50 6.1 – 7.3 [5,63]
compound 26 [PMID: 26267383] Hs Agonist 5.8 pEC50 56
pEC50 5.8 (EC50 1.616x10-6 M) [56]
Agonist Comments
Efficacy values for agonists are highly dependent on assay conditions and the readout.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H]SB-674042 Hs Antagonist 8.3 – 9.1 pKd 46,52-53
pKd 8.3 – 9.1 (Kd 5.03x10-9 – 7.4x10-10 M) [46,52-53]
suvorexant Hs Antagonist 9.3 pKi 17
pKi 9.3 (Ki 5.01x10-10 M) [17]
SB-649868 Hs Antagonist 9.1 pKi 19
pKi 9.1 (Ki 7.94x10-10 M) [19]
SB-674042 Hs Antagonist 8.7 – 9.1 pKi 46,52-53
pKi 8.7 – 9.1 (Ki 1.99x10-9 – 7.9x10-10 M) [46,52-53]
filorexant Hs Antagonist 8.6 pKi 79
pKi 8.6 (Ki 2.51x10-9 M) [79]
TCS 1102 Hs Antagonist 8.5 pKi 7
pKi 8.5 (Ki 3x10-9 M) [7]
lemborexant Hs Antagonist 8.2 pKi 82
pKi 8.2 (Ki 6x10-9 M) [82]
Description: In a radioligand binding assay
SB-410220 Hs Antagonist 7.7 pKi 46
pKi 7.7 [46]
SB-334867 Hs Antagonist 7.4 – 7.5 pKi 52,62
pKi 7.4 – 7.5 [52,62]
SB-408124 Hs Antagonist 7.2 – 7.6 pKi 46,52
pKi 7.2 – 7.6 (Ki 5.7x10-8 – 2.7x10-8 M) [46,52]
LSN2424100 Hs Antagonist 6.4 pKi 24
pKi 6.4 (Ki 3.93x10-7 M) [24]
JNJ-42847922 Rn Antagonist 6.2 pKi 10
pKi 6.2 (Ki 6.3x10-7 M) [10]
Description: In vitro radioligand binding assay
JNJ-42847922 Hs Antagonist 6.1 pKi 10
pKi 6.1 (Ki 7.94x10-7 M) [10]
Description: In vitro radioligand binding assay
MK-1064 Hs Antagonist 5.8 pKi 65
pKi 5.8 (Ki 1.584x10-6 M) [65]
compound 1 [PMID: 15261275] Hs Antagonist 5.3 – 6.1 pKi 54
pKi 5.3 – 6.1 [54]
JNJ-10397049 Hs Antagonist 5.3 – 5.8 pKi 54
pKi 5.3 – 5.8 [54]
MK-3697 Hs Antagonist 5.4 pKi 66
pKi 5.4 (Ki 3.6x10-6 M) [66]
compound 11 [PMID: 15261275] Hs Antagonist <5.3 pKi 54
pKi <5.3 (Ki >5.012x10-6 M) [54]
Description: Radioligand displacement assay using [125I]-orexin A as radio ligand.
ACT-335827 Hs Antagonist 8.1 – 8.2 pIC50 71
pIC50 8.1 – 8.2 (IC50 9x10-9 – 6x10-9 M) [71]
almorexant Hs Antagonist 7.9 pIC50 14
pIC50 7.9 (IC50 1.26x10-8 M) [14]
ACT-335827 Rn Antagonist 7.6 – 8.1 pIC50 71
pIC50 7.6 – 8.1 (IC50 2.5x10-8 – 7x10-9 M) [71]
ACT-462206 Hs Antagonist 7.2 pIC50 11
pIC50 7.2 (IC50 6x10-8 M) [11]
View species-specific antagonist tables
Primary Transduction Mechanisms
Transducer Effector/Response
Gs family
Gi/Go family
Gq/G11 family
Adenylate cyclase stimulation
Adenylate cyclase inhibition
Phospholipase C stimulation
Comments:  Association with the Gq family of transducers leads to phospholipase C stimulation (e.g. phospholipase C isoforms A2, C and D), and with the Gi family to inhibition and with the Gs family to stimulation, respectively, of adenylyl cyclase. Ca2+/non-selective cation influx also appears to rely on Gq. However, the signal transduction has not been investigated in detail in native neurons.
References:  2,29,31,34,40-41,44,46,50-51,55,59,68,70,74-75,77
Tissue Distribution
Pituitary: somatotroph cells.
Species:  Human
Technique:  Immunohistochemistry.
References:  9
Retina: ganglion cells, photoreceptor cells > amacrine cells, inner and outer plexiform layers.
Species:  Human
Technique:  Immunohistochemistry.
References:  69
Lung, skeletal muscle, kidney, testis > spleen > brain, liver.
Species:  Mouse
Technique:  RT-PCR
References:  16
CNS: highest levels found in the locus coeruleus > olfactory nuclei, piriform cortex, dentate gyrus of the hippocampus, bed nucleus of the stria terminalis, anterodorsal, centrolateral, reticular and ventral posterior thalamic nuclei, zona incerta, arcuate, paraventricular and periventricular hypothalamic nuclei, supraoptic nucleus, suprachiasmatic nucleus, dorsal tegmental nucleus, cochlear nucleus complex, facial nucleus, olivary complex, spinal cord, dorsal root ganglia.
Species:  Rat
Technique:  Immunohistochemistry.
References:  27
Olfactory system: olfactory mucosa (olfactory epithelium and lamina propria) > olfactory bulb, anterior olfactory nuclei and piriform cortex, hypothalamic and amygdala nuclei.
Species:  Rat
Technique:  immunocytochemistry.
References:  15
CNS: highest levels found in the ventromedial hypothalamic nucleus, tenia tecta, indusium griseum, septohippocampal nucleus, locus coeruleus.
Species:  Rat
Technique:  In situ hybridization.
References:  73
CNS: highest levels found in the hypothalamus, substantia nigra, thalamus.
Species:  Rat
Technique:  RT-PCR.
References:  27
Cerebral cortex, hippocampus, hypothalamus, several thalamic nuclei.
Species:  Rat
Technique:  Immunohistochemistry.
References:  6
Pancreatic islets.
Species:  Rat
Technique:  RT-PCR.
References:  58
Adrenal medulla.
Species:  Rat
Technique:  RT-PCR.
References:  49
Tissue Distribution Comments
For IHC studies, it is very important to note that selectivity issues have been raised regarding antibodies for the orexin receptors which may lead to false positive/negative results and as such, mRNA expression patterns provide important confirmatory results.
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays
Measurement of membrane conductance in locus coeruleus (LC) neurons endogenously expressing OX1 receptors.
Species:  Rat
Tissue:  LC neurons
Response measured:  Suppression of GIRK current.
References:  29
Measurement of cAMP levels in CHO-K1 cells transfected with the OX1 receptor.
Species:  Human
Tissue:  CHO-K1 cells
Response measured:  Stimulation (Gs and protein kinase C) and inhibition (Gi) of cAMP accumulation.
References:  32,40-41
Activation of ERK, p38 and JNK pathways in CHO-K1 cells transfected with the OX1 receptor
Species:  Human
Tissue:  CHO-K1 cells
Response measured:  Stimulation of ERK, p38 and JNK phosphorylation, programmed cell death.
References:  3-4,37
Ca2+ elevation in BIM hybridoma cells transfected with the OX1 receptor.
Species:  Rat
Tissue:  BIM cells
Response measured:  PTX-insensitive increase in [Ca2+].
References:  84
Activation of phospholipase D activity in CHO cells transfected with the OX1 receptor
Species:  Human
Tissue:  CHO
Response measured:  Phospholipase D activity (PtdBut generation assay) etc.
References:  34,36,40-41
Activation of phospholipase A2 and monoacylglycerol lipase-like enzyme-mediated arachidonic acid release in HEK293, CHO-K1 and neuro-2a cells transfected with the OX1 receptor
Species:  Human
Tissue:  HEK293, CHO-K1 and neuro-2a cells
Response measured:  Arachidonic acid and 2-arachidonoyl glycerol release, Ca2+ elevation
References:  61,74-75
Regulation of cell death and associated pathways in native and immortalised cell lines transfected to express the OX1 receptor
Species:  Human
Tissue:  CHO-S and -K1 and HT29-D4 cell lines, primary human colon carcinoma
Response measured:  Cell death
References:  4,23,67,76
Activation of phospholipase C in CHO-K1 cells transfected with the OX1 receptor
Species:  Human
Tissue:  CHO-K1 cells
Response measured:  Inositol phosphate release, PIP2 hydrolysis, IP3 elevation, diacylglycerol release, monoacylglycerol generation
References:  33-34,40-41,50,75
Measurement of membrane conductance in HEK 293 cells transfected with the OX1 receptor and GIRK channels.
Species:  Human
Tissue:  HEK 293 cells
Response measured:  Biphasic response: Initial phase of GIRK activation (both PTX-sensitive and -insensitive) followed by long-lasting GIRK inhibition (PTX-insensitive only).
References:  29
Activation of phospholipase C and Ca2+ elevation in neuro-2a and PC12 cells transfected with the OX1 receptor
Species:  Human
Tissue:  neuro-2a, PC12 cells
Response measured:  Inositol phosphate release, Ca2+ elevation
References:  30
Ca2+ elevation in CHO-K1 cells transfected with the OX1 receptor.
Species:  Human
Tissue:  CHO-K1 cells
Response measured:  Increase in [Ca2+]i via receptor-operated Ca2+ influx, (phospholipase C-mediated) Ca2+ release and store-operated Ca 2+ influx
References:  40,42,47,50,68,70,74-75
Physiological Functions
Modulation of feeding.
Species:  Rat
Tissue:  In vivo.
References:  26,64
Stimulation of water intake.
Species:  Rat
Tissue:  In vivo.
References:  45
Increase in respiratory drive.
Species:  Rat
Tissue:  Pre-Bötzinger-neurons and phrenic nuclei.
References:  83
Stimulation of behavioural arousal.
Species:  Rat
Tissue:  In vivo.
References:  20,35
Modulation of pain; analgesic and anti-hyperalgesic effects against a variety of noxious stimuli.
Species:  Rat
Tissue:  In vivo.
References:  8,80
Control of gastrointestinal function; modulation of gut motility and acid secretion.
Species:  Rat
Tissue:  In vivo.
References:  21-22
Regulation of haemodynamic responses; modulation of heart rate and blood pressure in anaesthetised rats.
Species:  Rat
Tissue:  In vivo.
References:  28
Modulation of rewarding behaviours and addiction.
Species:  Rat
Tissue:  In vivo.
References:  13,25
Facilitation of learning and memory. Targeted delivery of orexin-A to the dentate gyrus of anaesthetised rats produces an enhancement of LTP that is prevented by an OX1 receptor antagonist. Conversely, direct blockade of hippocampal OX1 receptors impairs spatial learning and memory in conscious rats.
Species:  Rat
Tissue:  In vivo.
References:  1,78
Enhancement of arousal and reduction in paradoxical and slow-wave sleep. Both an OX1 receptor-neutralising antibody and an OX1 receptor antagonist reverse the disruption of the sleep-wake cycle induced by centrally administered orexin-A.
Species:  Rat
Tissue:  In vivo.
References:  12
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Hcrtr1tm1Dgen Hcrtr1tm1Dgen/Hcrtr1tm1Dgen
involves: 129P2/OlaHsd * C57BL/6
MGI:2385650  MP:0002906 increased susceptibility to pharmacologically induced seizures
General Comments
No consequent differences in the molecular details of the signalling of the orexin receptor subtypes can be pointed out. In the CNS, both receptor subtypes regulate ion channel activity, most centrally leading to depolarization via activation of non-selective cation channels and inhibition of K+ channels [38,43,48]. Also, activation of Na+/Ca2+ exchanger has been reported. Orexin receptor activation has been implicated in modulation of synaptic plasticity. In native cells, cell lines and recombinant cells expressing heterologous orexin receptors, a wide set of molecular responses have been described. The immediate responses include activation of G proteins of Gq, Gi and Gs families and β-arrestin. Gq regulates at least receptor-operated Ca2+/non-selective cation influx and phospholipase C-mediated Ca2+ release, while Gi and Gs regulate adenylyl cyclase [39,41,43,48].
Orexin receptor subtypes form homo- and heteromeric complexes in recombinant systems. In addition, they are known to heteromerize with at least CB1 cannabinoid, κ opioid and CRF1 corticotropin receptors as well as with GPR103 [Reference: Kukkonen JP, Orexin/hypocretin Signaling, in Current Topics in Behavioral Neuroscience: Behavioral Neuroscience of Orexin/Hypocretin; ed. Andrew J Lawrence & Luis De Lecea, Springer; accepted for publication]. Little physiological significance has thus far been shown for this complex formation, except for a recent study showing complexes of OX1, CRF1 and sigma-1 receptors, which operate in orexin regulation of dopamine release in vetral tegmental area [57].

References

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1. Akbari E, Naghdi N, Motamedi F. (2006) Functional inactivation of orexin 1 receptors in CA1 region impairs acquisition, consolidation and retrieval in Morris water maze task. Behav Brain Res173: 47-52. [PMID:16815564]

2. Ammoun S, Holmqvist T, Shariatmadari R, Oonk HB, Detheux M, Parmentier M, Akerman KE, Kukkonen JP. (2003) Distinct recognition of OX1 and OX2 receptors by orexin peptides. J Pharmacol Exp Ther305: 507-514. [PMID:12606634]

3. Ammoun S, Johansson L, Ekholm ME, Holmqvist T, Danis AS, Korhonen L, Sergeeva OA, Haas HL, Akerman KE, Kukkonen JP. (2006) OX1 orexin receptors activate extracellular signal-regulated kinase in Chinese hamster ovary cells via multiple mechanisms: the role of Ca2+ influx in OX1 receptor signaling. Mol Endocrinol20: 80-89. [PMID:16141359]

4. Ammoun S, Lindholm D, Wootz H, Akerman KE, Kukkonen JP. (2006) G-protein-coupled OX1 orexin/hcrtr-1 hypocretin receptors induce caspase-dependent and -independent cell death through p38 mitogen-/stress-activated protein kinase. J Biol Chem281: 834-842. [PMID:16282319]

5. Asahi S, Egashira S, Matsuda M, Iwaasa H, Kanatani A, Ohkubo M, Ihara M, Morishima H. (2003) Development of an orexin-2 receptor selective agonist, [Ala(11), D-Leu(15)]orexin-B. Bioorg Med Chem Lett13: 111-113. [PMID:12467628]

6. Backberg M, Hervieu G, Wilson S, Meister B. (2002) Orexin receptor-1 (OX-R1) immunoreactivity in chemically identified neurons of the hypothalamus: focus on orexin targets involved in control of food and water intake. Eur J Neurosci15: 315-328. [PMID:11849298]

7. Bergman JM, Roecker AJ, Mercer SP, Bednar RA, Reiss DR, Ransom RW, Meacham Harrell C, Pettibone DJ, Lemaire W, Murphy KL et al.. (2008) Proline bis-amides as potent dual orexin receptor antagonists. Bioorg. Med. Chem. Lett.18 (4): 1425-30. [PMID:18207395]

8. Bingham S, Davey PT, Babbs AJ, Irving EA, Sammons MJ, Wyles M, Jeffrey P, Cutler L, Riba I, Johns A, Porter RA, Upton N, Hunter AJ, Parsons AA. (2001) Orexin-A, an hypothalamic peptide with analgesic properties. Pain92: 81-90. [PMID:11323129]

9. Blanco M, Lopez M, Garcia-Caballero T, Gallego R, Vazquez-Boquete A, Morel G, SenarIs R, Casanueva F, Dieguez C, Beiras A. (2001) Cellular localization of orexin receptors in human pituitary. J Clin Endocrinol Metab86: 1616-1619. [PMID:11443222]

10. Bonaventure P, Shelton J, Yun S, Nepomuceno D, Sutton S, Aluisio L, Fraser I, Lord B, Shoblock J, Welty N et al.. (2015) Characterization of JNJ-42847922, a Selective Orexin-2 Receptor Antagonist, as a Clinical Candidate for the Treatment of Insomnia. J. Pharmacol. Exp. Ther.354 (3): 471-82. [PMID:26177655]

11. Boss C, Roch-Brisbare C, Steiner MA, Treiber A, Dietrich H, Jenck F, von Raumer M, Sifferlen T, Brotschi C, Heidmann B et al.. (2014) Structure-activity relationship, biological, and pharmacological characterization of the proline sulfonamide ACT-462206: a potent, brain-penetrant dual orexin 1/orexin 2 receptor antagonist. ChemMedChem9 (11): 2486-96. [PMID:25147058]

12. Bourgin P, Huitron-Resendiz S, Spier AD, Fabre V, Morte B, Criado JR, Sutcliffe JG, Henriksen SJ, De Lecea L. (2000) Hypocretin-1 modulates rapid eye movement sleep through activation of locus coeruleus neurons. J Neurosci20: 7760-7765. [PMID:11027239]

13. Boutrel B, Kenny PJ, Specio SE, Martin-Fardon R, Markou A, Koob GF, De Lecea L. (2005) Role for hypocretin in mediating stress-induced reinstatement of cocaine-seeking behavior. Proc Natl Acad Sci U S A102: 19168-19173. [PMID:16357203]

14. Brisbare-Roch C, Dingemanse J, Koberstein R, Hoever P, Aissaoui H, Flores S, Mueller C, Nayler O, van Gerven J, de Haas SL, Hess P, Qiu C, Buchmann S, Scherz M, Weller T, Fischli W, Clozel M, Jenck F. (2007) Promotion of sleep by targeting the orexin system in rats, dogs and humans. Nat. Med.13 (2): 150-5. [PMID:17259994]

15. Caillol M, Aioun J, Baly C, Persuy MA, Salesse R. (2003) Localization of orexins and their receptors in the rat olfactory system: possible modulation of olfactory perception by a neuropeptide synthetized centrally or locally. Brain Res960: 48-61. [PMID:12505657]

16. Chen J, Randeva HS. (2004) Genomic organization of mouse orexin receptors: characterization of two novel tissue-specific splice variants. Mol Endocrinol18: 2790-2804. [PMID:15256537]

17. Cox CD, Breslin MJ, Whitman DB, Schreier JD, McGaughey GB, Bogusky MJ, Roecker AJ, Mercer SP, Bednar RA, Lemaire W, Bruno JG, Reiss DR, Harrell CM, Murphy KL, Garson SL, Doran SM, Prueksaritanont T, Anderson WB, Tang C, Roller S, Cabalu TD, Cui D, Hartman GD, Young SD, Koblan KS, Winrow CJ, Renger JJ, Coleman PJ. (2010) Discovery of the dual orexin receptor antagonist [(7R)-4-(5-chloro-1,3-benzoxazol-2-yl)-7-methyl-1,4-diazepan-1-yl][5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl]methanone (MK-4305) for the treatment of insomnia. J. Med. Chem.53 (14): 5320-32. [PMID:20565075]

18. Darker JG, Porter RA, Eggleston DS, Smart D, Brough SJ, Sabido-David C, Jerman JC. (2001) Structure-activity analysis of truncated orexin-A analogues at the orexin-1 receptor. Bioorg Med Chem Lett11: 737-740. [PMID:11266181]

19. Di Fabio R, Pellacani A, Faedo S, Roth A, Piccoli L, Gerrard P, Porter RA, Johnson CN, Thewlis K, Donati D et al.. (2011) Discovery process and pharmacological characterization of a novel dual orexin 1 and orexin 2 receptor antagonist useful for treatment of sleep disorders. Bioorg. Med. Chem. Lett.21 (18): 5562-7. [PMID:21831639]

20. Duxon MS, Stretton J, Starr K, Jones DN, Holland V, Riley G, Jerman J, Brough S, Smart D, Johns A, Chan W, Porter RA, Upton N. (2001) Evidence that orexin-A-evoked grooming in the rat is mediated by orexin-1 (OX1) receptors, with downstream 5-HT2C receptor involvement. Psychopharmacology (Berl)153: 203-209. [PMID:11205420]

21. Ehrström M, Levin F, Kirchgessner AL, Schmidt PT, Hilsted LM, Grybäck P, Jacobsson H, Hellström PM, Näslund E. (2005) Stimulatory effect of endogenous orexin A on gastric emptying and acid secretion independent of gastrin. Regul Pept132: 9-16. [PMID:16125803]

22. Ehrström M, Näslund E, Ma J, Kirchgessner AL, Hellström PM. (2003) Physiological regulation and NO-dependent inhibition of migrating myoelectric complex in the rat small bowel by OXA. Am J Physiol Gastrointest Liver Physiol285: G688-G695. [PMID:12816759]

23. El Firar A, Voisin T, Rouyer-Fessard C, Ostuni MA, Couvineau A, Laburthe M. (2009) Discovery of a functional immunoreceptor tyrosine-based switch motif in a 7-transmembrane-spanning receptor: role in the orexin receptor OX1R-driven apoptosis. FASEB J.23 (12): 4069-80. [PMID:19661287]

24. Fitch TE, Benvenga MJ, Jesudason CD, Zink C, Vandergriff AB, Menezes MM, Schober DA, Rorick-Kehn LM. (2014) LSN2424100: a novel, potent orexin-2 receptor antagonist with selectivity over orexin-1 receptors and activity in an animal model predictive of antidepressant-like efficacy. Front Neurosci8: 5. [PMID:24478625]

25. Harris GC, Wimmer M, Aston-Jones G. (2005) A role for lateral hypothalamic orexin neurons in reward seeking. Nature437: 556-559. [PMID:16100511]

26. Haynes AC, Jackson B, Chapman H, Tadayyon M, Johns A, Porter RA, Arch JR. (2000) A selective orexin-1 receptor antagonist reduces food consumption in male and female rats. Regul Pept96: 45-51. [PMID:11102651]

27. Hervieu GJ, Cluderay JE, Harrison DC, Roberts JC, Leslie RA. (2001) Gene expression and protein distribution of the orexin-1 receptor in the rat brain and spinal cord. Neuroscience103: 777-797. [PMID:11274794]

28. Hirota K, Kushikata T, Kudo M, Kudo T, Smart D, Matsuki A. (2003) Effects of central hypocretin-1 administration on hemodynamic responses in young-adult and middle-aged rats. Brain Res981: 143-150. [PMID:12885435]

29. Hoang QV, Bajic D, Yanagisawa M, Nakajima S, Nakajima Y. (2003) Effects of orexin (hypocretin) on GIRK channels. J Neurophysiol90: 693-702. [PMID:12702704]

30. Holmqvist T, Akerman KE, Kukkonen JP. (2001) High specificity of human orexin receptors for orexins over neuropeptide Y and other neuropeptides. Neurosci Lett305: 177-180. [PMID:11403934]

31. Holmqvist T, Akerman KE, Kukkonen JP. (2002) Orexin signaling in recombinant neuron-like cells. FEBS Lett.526 (1-3): 11-4. [PMID:12208495]

32. Holmqvist T, Johansson L, Ostman M, Ammoun S, Akerman KE, Kukkonen JP. (2005) OX1 orexin receptors couple to adenylyl cyclase regulation via multiple mechanisms. J Biol Chem280: 6570-6579. [PMID:15611118]

33. Johansson L, Ekholm ME, Kukkonen JP. (2007) Regulation of OX1 orexin/hypocretin receptor-coupling to phospholipase C by Ca2+ influx. Br. J. Pharmacol.150 (1): 97-104. [PMID:17115071]

34. Johansson L, Ekholm ME, Kukkonen JP. (2008) Multiple phospholipase activation by OX(1) orexin/hypocretin receptors. Cell. Mol. Life Sci.65 (12): 1948-56. [PMID:18488139]

35. Jones DN, Gartlon J, Parker F, Taylor SG, Routledge C, Hemmati P, Munton RP, Ashmeade TE, Hatcher JP, Johns A, Porter RA, Hagan JJ, Hunter AJ, Upton N. (2001) Effects of centrally administered orexin-B and orexin-A: a role for orexin-1 receptors in orexin-B-induced hyperactivity. Psychopharmacology (Berl)153: 210-218. [PMID:11205421]

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Christopher J. Winrow, Paul Coleman, Luis de Lecea, Thomas Kilduff, Jyrki P. Kukkonen, Rod Porter, John Renger, Jerome M Siegel, Gregor Sutcliffe, Neil Upton.
Orexin receptors: OX1 receptor. Last modified on 23/02/2017. Accessed on 24/07/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=321.