Gene Symbol: OX2R
Description: hypocretin receptor 2
Alias: OX2R, orexin receptor type 2, hypocretin (orexin) receptor 2, hypocretin receptor type 2, orexin type-2 receptor, ox-2-R, ox2-R
Species: human
Products:     OX2R

Top Publications

  1. Rainero I, Gallone S, Valfrè W, Ferrero M, Angilella G, Rivoiro C, et al. A polymorphism of the hypocretin receptor 2 gene is associated with cluster headache. Neurology. 2004;63:1286-8 pubmed
    ..Homozygosity for the G allele was associated with an increased disease risk (OR: 6.79, 95% CI, 2.25 to 22.99). The data suggest that the HCRTR2 gene or a linked locus significantly modulates the risk for cluster headache. ..
  2. Schurks M, Kurth T, Geissler I, Tessmann G, Diener H, Rosskopf D. Cluster headache is associated with the G1246A polymorphism in the hypocretin receptor 2 gene. Neurology. 2006;66:1917-9 pubmed
    ..The genotype and allele distribution varied significantly between patients and controls. Homozygous carriers of the G-allele had a twofold increase in risk for CH (OR 1.97; 95% CI 1.32 to 2.92; p = 0.0007). ..
  3. de Lecea L, Kilduff T, Peyron C, Gao X, Foye P, Danielson P, et al. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci U S A. 1998;95:322-7 pubmed
    ..One of the Hcrt peptides was excitatory when applied to cultured, synaptically coupled hypothalamic neurons, but not hippocampal neurons. These observations suggest that the hypocretins function within the CNS as neurotransmitters. ..
  4. Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli R, Tanaka H, et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell. 1998;92:573-85 pubmed
    ..prepro-orexin mRNA level is up-regulated upon fasting, suggesting a physiological role for the peptides as mediators in the central feedback mechanism that regulates feeding behavior. ..
  5. Tang J, Chen J, Ramanjaneya M, Punn A, Conner A, Randeva H. The signalling profile of recombinant human orexin-2 receptor. Cell Signal. 2008;20:1651-61 pubmed publisher
    ..and orexin-B orchestrate their diverse central and peripheral effects via two G-protein coupled receptors, OX1R and OX2R, which activate multiple G-proteins...
  6. Blais A, Drouin G, Chaumontet C, Voisin T, Couvelard A, Even P, et al. Impact of Orexin-A Treatment on Food Intake, Energy Metabolism and Body Weight in Mice. PLoS ONE. 2017;12:e0169908 pubmed publisher
    ..HCRT), and Y2 and Y5 neuropeptide Y, MC4 (melanocortin), OX1 and OX2 orexin receptors (Y2R, Y5R, MC4R, OX1R and OX2R, respectively) was also explored...
  7. Gonzalez B, Torres O, Jayanthi S, Gomez N, Sosa M, Bernardi A, et al. The effects of single-dose injections of modafinil and methamphetamine on epigenetic and functional markers in the mouse medial prefrontal cortex: potential role of dopamine receptors. Prog Neuropsychopharmacol Biol Psychiatry. 2019;88:222-234 pubmed publisher
  8. Thompson M, Sakurai T, Rainero I, Maj M, Kukkonen J. Orexin Receptor Multimerization versus Functional Interactions: Neuropharmacological Implications for Opioid and Cannabinoid Signalling and Pharmacogenetics. Pharmaceuticals (Basel). 2017;10: pubmed publisher
    ..Evidence for functional interactions and/or heterodimerization between wild-type and variant orexin receptors and opioid and cannabinoid receptors is discussed in the context of its relevance to depression and epilepsy. ..
  9. Kitajima S, Iwata Y, Furuichi K, Sagara A, Shinozaki Y, Toyama T, et al. Messenger RNA expression profile of sleep-related genes in peripheral blood cells in patients with chronic kidney disease. Clin Exp Nephrol. 2016;20:218-25 pubmed publisher
    ..These data indicate that the expression of sleep-related genes in PBCs of CKD patients may be associated with sleep abnormalities. ..

More Information

Publications157 found, 100 shown here

  1. Takenoshita S, Sakai N, Chiba Y, Matsumura M, Yamaguchi M, Nishino S. An overview of hypocretin based therapy in narcolepsy. Expert Opin Investig Drugs. 2018;27:389-406 pubmed publisher
    ..If this option is effective in humans, hypocretin cell transplants or gene therapy technology may become realistic in the future. ..
  2. Lane J, Liang J, Vlasac I, Anderson S, Bechtold D, Bowden J, et al. Genome-wide association analyses of sleep disturbance traits identify new loci and highlight shared genetics with neuropsychiatric and metabolic traits. Nat Genet. 2017;49:274-281 pubmed publisher
    ..20, P = 3.12 × 10-9; waist circumference: rg = 0.20, P = 2.12 × 10-7). ..
  3. Lei K, Wegner S, Yu J, Hopf F. Orexin-1 receptor blockade suppresses compulsive-like alcohol drinking in mice. Neuropharmacology. 2016;110:431-437 pubmed publisher
    ..In addition, the OX2R antagonist TCS-OX2-29 (3 or 10 mg/kg) did not alter intake of alcohol with or without quinine...
  4. Howland R. Suvorexant: a novel therapy for the treatment of insomnia. J Psychosoc Nurs Ment Health Serv. 2014;52:23-6 pubmed publisher
    Suvorexant is a pharmacologically novel dual antagonist of orexin receptors OX1R and OX2R, which has an effect that promotes sleep by reducing arousal and wakefulness...
  5. Ahmed S, Steinman L. Mechanistic insights into influenza vaccine-associated narcolepsy. Hum Vaccin Immunother. 2016;12:3196-3201 pubmed publisher
  6. Scott M, Marcus J, Pettersen A, Birnbaum S, Mochizuki T, Scammell T, et al. Hcrtr1 and 2 signaling differentially regulates depression-like behaviors. Behav Brain Res. 2011;222:289-94 pubmed publisher
    ..These studies suggest that the balance of orexin action at either the hcrtr1 or the hcrtr2 receptor produces an anti-depressant or pro-depressant like effect, depending on the receptor subtype activated. ..
  7. Qiao S, Zhou W, Liu L, Zhang D, Zhong Y. Orexin-A Suppresses Signal Transmission to Dopaminergic Amacrine Cells From Outer and Inner Retinal Photoreceptors. Invest Ophthalmol Vis Sci. 2017;58:4712-4721 pubmed publisher
    ..Our results suggest that orexins could influence visual function via the dopaminergic system in the mammalian retina. ..
  8. Steinman L, Ahmed S. Response to comment on "Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2". Sci Transl Med. 2015;7:314lr2 pubmed publisher
    ..They present data on the distribution of hypocretin (HCRT) (also known as orexin) receptors in the brain of an engineered mouse developed by them. ..
  9. Hu Y, Shmygelska A, Tran D, Eriksson N, Tung J, Hinds D. GWAS of 89,283 individuals identifies genetic variants associated with self-reporting of being a morning person. Nat Commun. 2016;7:10448 pubmed publisher
    ..Our findings reinforce current understanding of circadian biology and will guide future studies. ..
  10. He C, Chen Q, Ye J, Li C, Yang L, Zhang J, et al. Functional inactivation of hypocretin 1 receptors in the medial prefrontal cortex affects the pyramidal neuron activity and gamma oscillations: An in vivo multiple-channel single-unit recording study. Neuroscience. 2015;297:1-10 pubmed publisher
    ..Together, these data indicate that endogenous hypocretins acting on the Hcrtr1 are required for the normal neural activity in the mPFC in vivo, and thus might directly contribute cortical arousal and mPFC-dependent cognitive processes. ..
  11. Heifetz A, Bodkin M, Biggin P. Discovery of the First Selective, Nonpeptidic Orexin 2 Receptor Agonists. J Med Chem. 2015;58:7928-30 pubmed publisher
    In this issue, Nagase and colleagues report the discovery of the first selective nonpeptidic orexin 2 receptor (OX2R) agonists...
  12. Roecker A, Mercer S, Bergman J, Gilbert K, Kuduk S, Harrell C, et al. Discovery of diazepane amide DORAs and 2-SORAs enabled by exploration of isosteric quinazoline replacements. Bioorg Med Chem Lett. 2015;25:4992-4999 pubmed publisher
    ..chemistry used to produce these DORAs yielded isomeric pyrimidine-containing diazepane amides possessing selective OX2R antagonist (2-SORA) profiles...
  13. Futamura A, Nozawa D, Araki Y, Tamura Y, Tokura S, Kawamoto H, et al. Identification of highly selective and potent orexin receptor 1 antagonists derived from a dual orexin receptor 1/2 antagonist based on the structural framework of pyrazoylethylbenzamide. Bioorg Med Chem. 2017;25:5203-5215 pubmed publisher
    ..01nM and a 265-fold selectivity for orexin receptor 1 over orexin receptor 2. ..
  14. Kuduk S, Skudlarek J, DiMarco C, Bruno J, Pausch M, O Brien J, et al. Identification of MK-8133: An orexin-2 selective receptor antagonist with favorable development properties. Bioorg Med Chem Lett. 2015;25:2488-92 pubmed publisher
    ..to the dual orexin receptor antagonist filorexant were transformed into compounds that were selective for the OX2R subtype...
  15. Dobrzyn K, Smolinska N, Kiezun M, Szeszko K, Rytelewska E, Kisielewska K, et al. The in vitro effect of progesterone on the orexin system in porcine uterine tissues during early pregnancy. Acta Vet Scand. 2018;60:76 pubmed publisher
    ..of orexin receptor 1 (OX1R) protein at nearly all times analyzed, whereas the expression of orexin receptor 2 (OX2R) protein was inhibited only on days 15 to 16 of gestation...
  16. Fujisawa S, Komatsubara M, Ogura Ochi K, Tsukamoto Yamauchi N, Toma K, Inagaki K, et al. Orexin A modulates prolactin production by regulating BMP-4 activity in rat pituitary lactotorope cells. Peptides. 2019;113:35-40 pubmed publisher
    ..Orexin type 1 receptor (OX1R), but not type 2 receptor (OX2R), was predominantly expressed in GH3 cells...
  17. Fartootzadeh R, Azizi F, Alaei H, Reisi P. Orexin type-2 receptor blockade prevents the nicotine-induced excitation of nucleus accumbens core neurons in rats: An electrophysiological perspective. Pharmacol Rep. 2019;71:361-366 pubmed publisher
    ..The role of orexin-2 receptor (OX2R) in the regulation of NAcc neural activity in response to nicotine has not yet been studied...
  18. Imperatore R, Cristino L. Role of Orexin-B/Orexin 2 receptor in myocardial protection. Clin Sci (Lond). 2019;133:853-857 pubmed publisher
    ..Indeed, OR-B, but not OR-A, by acting through orexin receptor-2 (OX2R), exerts direct cardioprotective effects in heart failure models...
  19. Roecker A, Mercer S, Harrell C, Garson S, Fox S, Gotter A, et al. Discovery of dual orexin receptor antagonists with rat sleep efficacy enabled by expansion of the acetonitrile-assisted/diphosgene-mediated 2,4-dichloropyrimidine synthesis. Bioorg Med Chem Lett. 2014;24:2079-85 pubmed publisher
    Recent clinical studies have demonstrated that dual orexin receptor antagonists (OX1R and OX2R antagonists or DORAs) represent a novel treatment option for insomnia patients...
  20. Satoh A, Brace C, Rensing N, Cliften P, Wozniak D, Herzog E, et al. Sirt1 extends life span and delays aging in mice through the regulation of Nk2 homeobox 1 in the DMH and LH. Cell Metab. 2013;18:416-30 pubmed publisher
    ..in the dorsomedial and lateral hypothalamic nuclei (DMH and LH, respectively), through increased orexin type 2 receptor (Ox2r) expression...
  21. Rattanathanawan K, Busarakumtragul P, Thongket P, Neruntarat C, Sukhumsirichart W. Association of Single Nucleotide Polymorphisms of Endothelin, Orexin and Vascular Endothelial Growth Factor Receptor Genes with Obstructive Sleep Apnea among Thai Ethnic. J Med Assoc Thai. 2016;99 Suppl 8:S150-S157 pubmed
    ..investigated the association between single nucleotide polymorphisms (SNPs) in endothelin (EDNRA), orexin (OX1R, OX2R) and vascular endothelial growth factor (VEGFR1) receptor genes with risk of OSA in Thai population...
  22. Cai Z, Liu H, Wang L, Li X, Bai L, Gan X, et al. Molecular Evolutionary Analysis of the HCRTR Gene Family in Vertebrates. Biomed Res Int. 2018;2018:8120263 pubmed publisher
    ..Our study gains insight into the molecular evolution process of HCRTR gene family, which contributes to the further study of the system. ..
  23. Schmeichel B, Barbier E, Misra K, Contet C, Schlosburg J, Grigoriadis D, et al. Hypocretin receptor 2 antagonism dose-dependently reduces escalated heroin self-administration in rats. Neuropsychopharmacology. 2015;40:1123-9 pubmed publisher
  24. Waters B, Hara K, Ikematsu N, Takayama M, Matsusue A, Kashiwagi M, et al. Tissue Distribution of Suvorexant in Three Forensic Autopsy Cases. J Anal Toxicol. 2018;42:276-283 pubmed publisher
    ..a dual orexin receptor antagonist that promotes sleep by inhibiting the binding of orexin neurons to the OX1R and OX2R receptors...
  25. Ji M, Zhang X, Chen Z, Wang J, Zhu J. Orexin prevents depressive-like behavior by promoting stress resilience. Mol Psychiatry. 2019;24:282-293 pubmed publisher
    ..Two orexin receptors, OX1R and OX2R, and their downstream Na+-Ca2+ exchanger and L-type Ca2+ channel co-mediate the ..
  26. McConn B, Gilbert E, Cline M. Fasting and refeeding induce differential changes in hypothalamic mRNA abundance of appetite-associated factors in 7 day-old Japanese quail, Coturnix japonica. Comp Biochem Physiol A Mol Integr Physiol. 2018;227:60-67 pubmed publisher
    ..Most genes remained elevated or downregulated after refeeding, suggesting that there was a time lag for transcription to respond to compensatory feeding. ..
  27. Azizbeigi R, Haghparast A. Involvement of orexin-2 receptor in the ventral tegmental area in stress- and drug priming-induced reinstatement of conditioned place preference in rats. Neurosci Lett. 2019;696:121-126 pubmed publisher
    ..model has been used to examine the effects of intra-VTA administration of TCS-OX2-29, an orexin-2 receptor (OX2R) antagonist, on drug priming- and forced swim stress (FSS)-induced reinstatement of morphine-induced conditioned ..
  28. Patel V, Karteris E, Chen J, Kyrou I, Mattu H, Dimitriadis G, et al. Functional cardiac orexin receptors: role of orexin-B/orexin 2 receptor in myocardial protection. Clin Sci (Lond). 2018;132:2547-2564 pubmed publisher
    ..A specific orexin receptor-2 (OX2R) agonist ([Ala11, d-Leu15]-Orexin B) exerted similar effects as OR-B, whereas a specific ..
  29. Vassalli A, Li S, Tafti M. Comment on "Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2". Sci Transl Med. 2015;7:314le2 pubmed publisher
    ..now show that hypocretin neurons (whose loss causes narcolepsy) do not express hypocretin autoreceptors, raising questions to the interpretation of Ahmed et al.'s findings. ..
  30. Wang Q, Wang C, Cheng B, Yang C, Bai B, Chen J. Signaling transduction regulated by 5-hydroxytryptamine 1A receptor and orexin receptor 2 heterodimers. Cell Signal. 2019;54:46-58 pubmed publisher
    As G-protein-coupled receptors (GPCRs), 5-hydroxytryptamine 1A receptor (5-HT1AR) and orexin receptor 2 (OX2R) regulate the levels of the cellular downstream molecules...
  31. Rojczyk E, Pałasz A, Wiaderkiewicz R. Effect of short and long-term treatment with antipsychotics on orexigenic/anorexigenic neuropeptides expression in the rat hypothalamus. Neuropeptides. 2015;51:31-42 pubmed publisher
    ..Y (NPY), NPY receptor type 1 (Y1R), preproorexin (PPOX), orexin A, orexin receptor type 1 (OX1R) and 2 (OX2R), nucleobindin 2 (NUCB2), nesfatin-1, proopiomelanocortin (POMC), alpha-melanotropin (α-MSH) and melanocortin ..
  32. Giannoccaro M, Waters P, Pizza F, Liguori R, Plazzi G, Vincent A. Antibodies Against Hypocretin Receptor 2 Are Rare in Narcolepsy. Sleep. 2017;40: pubmed publisher
    ..Low levels of IgG1 or IgG3 antibodies against HCRTR2 were found in 3 of 61 patients with narcolepsy, although only 1 presented with full-blown NT1. HCRTR2-Abs are not common in narcolepsy unrelated to vaccination. ..
  33. Li G, Zhang K, Wang L, Cao C, Fang R, Liu P, et al. The preliminary investigation of orexigenic hormone gene polymorphisms on posttraumatic stress disorder symptoms. Psychoneuroendocrinology. 2019;100:131-136 pubmed publisher
    ..These current findings expand our knowledge of physiological function of the orexigenic hormone system, and suggest its involvement in development of fear-related mental disorders such as PTSD. ..
  34. Smolinska N, Kiezun M, Dobrzyn K, Szeszko K, Maleszka A, Kaminski T. Expression of the orexin system in the porcine uterus, conceptus and trophoblast during early pregnancy. Animal. 2015;9:1820-31 pubmed publisher
    ..Those peptides bind and activate two G protein-coupled receptors: orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R)...
  35. Sun M, Wang W, Li Q, Yuan T, Weng W. Orexin A may suppress inflammatory response in fibroblast-like synoviocytes. Biomed Pharmacother. 2018;107:763-768 pubmed publisher
    ..by inhibiting oxidative stress and inflammatory response via their type 1 and 2 receptors (OX1R and OX2R)...
  36. Messal N, Fernandez N, Dayot S, Gratio V, Nicole P, Prochasson C, et al. Ectopic expression of OX1R in ulcerative colitis mediates anti-inflammatory effect of orexin-A. Biochim Biophys Acta Mol Basis Dis. 2018;1864:3618-3628 pubmed publisher
    ..and are involved in sleep/wake control, which is mediated by two G protein-coupled receptor subtypes, OX1R and OX2R. Ulcerative colitis (UC) is an inflammatory bowel disease, (IBD) which is characterized by long-lasting ..
  37. Wang Z, Liu S, Kakizaki M, Hirose Y, Ishikawa Y, Funato H, et al. Orexin/hypocretin activates mTOR complex 1 (mTORC1) via an Erk/Akt-independent and calcium-stimulated lysosome v-ATPase pathway. J Biol Chem. 2014;289:31950-9 pubmed publisher
    ..cell lines that express the G protein-coupled receptors (GPCRs), orexin 1 receptor (OX1R) or orexin 2 receptor (OX2R)...
  38. Varricchio E, Russo F, Coccia E, Turchini G, Francis D, Paolucci M. The orexinergic system in rainbow trout Oncorhynchus mykiss and its regulation by dietary lipids. Microsc Res Tech. 2015;78:707-14 pubmed publisher
    In this study, we report the distribution of orexin A (OXA), orexin B (OXB), and orexin receptor (OX2R) immunoreactive (ir) cells in the hypothalamus and gastrointestinal tract of Oncorhynchus mykiss fed diets with different dietary fatty ..
  39. Zheng C, Deng Q, Liu L, Wang M, Zhang G, Sheng W, et al. Orexin-A differentially modulates AMPA-preferring responses of ganglion cells and amacrine cells in rat retina. Neuropharmacology. 2015;93:80-93 pubmed publisher
    By activating their receptors (OX1R and OX2R) orexin-A/B regulate wake/sleeping states, feeding behaviors, but the function of these peptides in the retina remains unknown...
  40. Mavanji V, Perez Leighton C, Kotz C, Billington C, Parthasarathy S, Sinton C, et al. Promotion of Wakefulness and Energy Expenditure by Orexin-A in the Ventrolateral Preoptic Area. Sleep. 2015;38:1361-70 pubmed publisher
    ..We also tested whether pretreatment with a dual orexin receptor antagonist (DORA, TCS-1102) or an OX2R antagonist (JNJ-10397049) blocked the effects of orexin-A on the sleep/wake cycle or SPA, respectively...
  41. Wang D, Ren H, Li C, Liu F, Wang G, Shi F, et al. Orexin A prevents degradation of the articular matrixes in human primary chondrocyte culture. Mol Immunol. 2018;101:102-107 pubmed publisher
    ..via activation of its specific G-protein coupled receptors, orexin-1 receptor (OX1R) and orexin-2 receptor (OX2R)...
  42. Huang S, Li T, Lee Y, Dai Y, Chen Y, Hwang L. Role of the orexin 2 receptor in palatable-food consumption-associated cardiovascular reactivity in spontaneously hypertensive rats. Sci Rep. 2018;8:12703 pubmed publisher
    ..Central orexin 2 receptor (OX2R) blockade attenuated sucrose-agar consumption-associated cardiovascular response only in SHRs...
  43. Johnson P, Federici L, Fitz S, Renger J, Shireman B, Winrow C, et al. OREXIN 1 AND 2 RECEPTOR INVOLVEMENT IN CO2 -INDUCED PANIC-ASSOCIATED BEHAVIOR AND AUTONOMIC RESPONSES. Depress Anxiety. 2015;32:671-83 pubmed publisher
    ..Although the two cognate orexin receptors are colocalized in many brain regions, the orexin 2 receptor (OX2R) most robustly maps to the histaminergic wake-promoting region, while the orexin 1 receptor (OX1R) distribution is ..
  44. Goudarzi E, Elahdadi Salmani M, Lashkarbolouki T, Goudarzi I. Hippocampal orexin receptors inactivation reduces PTZ induced seizures of male rats. Pharmacol Biochem Behav. 2015;130:77-83 pubmed publisher
    ..Orexin 1 receptor (OX1R) antagonist (SB) and OX2R antagonist (TCS) were administrated bilaterally through separate cannulae into both hippocampi...
  45. Heifetz A, Aldeghi M, Chudyk E, Fedorov D, Bodkin M, Biggin P. Using the fragment molecular orbital method to investigate agonist-orexin-2 receptor interactions. Biochem Soc Trans. 2016;44:574-81 pubmed publisher
    ..FMO) quantum mechanics (QM) method to explore the interactions and selectivity of the human orexin-2 receptor (OX2R) and its recently discovered nonpeptidic agonists...
  46. Esmaeili M, Reisi Z, Ezzatpanah S, Haghparast A. Role of orexin-2 and CB1 receptors within the periaqueductal gray matter in lateral hypothalamic-induced antinociception in rats. Behav Pharmacol. 2017;28:83-89 pubmed publisher
    Orexin plays an important role in pain modulation. Orexin-1 and orexin-2 receptors (Ox1r and Ox2r) are found at high density in the ventrolateral periaqueductal gray matter (vlPAG)...
  47. Katsarou M, Papasavva M, Latsi R, Toliza I, Gkaros A, Papakonstantinou S, et al. Population-Based Analysis of Cluster Headache-Associated Genetic Polymorphisms. J Mol Neurosci. 2018;65:367-376 pubmed publisher
    ..Cluster headache pathophysiology and pharmacotherapy response may be affected by genetic factors, indicating the significant role of genotyping in the overall treatment effectiveness of cluster headaches. ..
  48. Dong Y, Li M, Wang S, Dong Y, Zhao H, Dai Z. Xingshentongqiao decoction mediates proliferation, apoptosis, orexin-A receptor and orexin-B receptor messenger ribonucleic acid expression and represses mitogen-activated protein kinase signaling. Chin Med J (Engl). 2015;128:98-104 pubmed publisher
    ..on SH-SY5Y cell proliferation, apoptosis, and HCRT receptor 1/2 (orexin receptor 1 [OX1R] and orexin receptor 2 [OX2R]) expression. The signaling pathways involved in these processes were also assessed...
  49. Sabetghadam A, Grabowiecka Nowak A, Kania A, Gugula A, Blasiak E, Blasiak T, et al. Melanin-concentrating hormone and orexin systems in rat nucleus incertus: Dual innervation, bidirectional effects on neuron activity, and differential influences on arousal and feeding. Neuropharmacology. 2018;139:238-256 pubmed publisher
    ..Our findings identify MCH and orexin inputs onto divergent NI populations which may differentially influence arousal and motivated behaviours. ..
  50. Rainero I, Gallone S, Rubino E, Ponzo P, Valfrè W, Binello E, et al. Haplotype analysis confirms the association between the HCRTR2 gene and cluster headache. Headache. 2008;48:1108-14 pubmed publisher
    ..In addition, we suggest that the V308I substitution of the HCRTR2 may interfere with the dimerization process of the receptor, thereby influencing its functional activity. ..
  51. Raheem I, Breslin M, Bruno J, Cabalu T, Cooke A, Cox C, et al. Discovery of piperidine ethers as selective orexin receptor antagonists (SORAs) inspired by filorexant. Bioorg Med Chem Lett. 2015;25:444-50 pubmed publisher
    Highly selective orexin receptor antagonists (SORAs) of the orexin 2 receptor (OX2R) have become attractive targets both as potential therapeutics for insomnia as well as biological tools to help further elucidate the underlying ..
  52. Iwasa T, Matsuzaki T, Munkhzaya M, Tungalagsuvd A, Kuwahara A, Yasui T, et al. Developmental changes in the hypothalamic mRNA levels of prepro-orexin and orexin receptors and their sensitivity to fasting in male and female rats. Int J Dev Neurosci. 2015;46:51-4 pubmed publisher
    ..The developmental changes in the hypothalamic mRNA levels of pp-prexin and the orexin receptors OX1R and OX2R and their sensitivity to fasting were evaluated in both male and female rats...
  53. Farzinpour Z, Taslimi Z, Azizbeigi R, Karimi Haghighi S, Haghparast A. Involvement of orexinergic receptors in the nucleus accumbens, in the effect of forced swim stress on the reinstatement of morphine seeking behaviors. Behav Brain Res. 2019;356:279-287 pubmed publisher
    ..The extinguished rats received intra-NAc injection of SB334867 as OX1R antagonist or TCSOX229 as OX2R antagonist before effective priming dose injection of morphine (1 mg/kg; sc)...
  54. Beig M, Dampney B, Carrive P. Both Ox1r and Ox2r orexin receptors contribute to the cardiovascular and locomotor components of the novelty stress response in the rat. Neuropharmacology. 2015;89:146-56 pubmed publisher
    ..Thus, Almorexant, a dual receptor antagonist that blocks the two known orexin receptors, Ox1R and Ox2R, reduces these responses...
  55. Jäntti M, Mandrika I, Kukkonen J. Human orexin/hypocretin receptors form constitutive homo- and heteromeric complexes with each other and with human CB1 cannabinoid receptors. Biochem Biophys Res Commun. 2014;445:486-90 pubmed publisher
    ..As orexin receptors efficiently signal via endocannabinoid production to CB1 receptors, dimerization could be an effective way of forming signal complexes with optimal cannabinoid concentrations available for cannabinoid receptors. ..
  56. Lee Y, Tsai M, Li T, Dai Y, Huang S, Hwang L. Spontaneously hypertensive rats have more orexin neurons in the hypothalamus and enhanced orexinergic input and orexin 2 receptor-associated nitric oxide signalling in the rostral ventrolateral medulla. Exp Physiol. 2015;100:993-1007 pubmed publisher
    What is the central question of this study? Our previous study demonstrates that elevated orexin 2 receptor (OX2R) activity within the rostral ventrolateral medulla (RVLM) contributes to hypertension in spontaneously hypertensive rats (..
  57. Mohammad Ahmadi Soleimani S, Azizi H, Mirnajafi Zadeh J, Semnanian S. Orexin type 1 receptor antagonism in rat locus coeruleus prevents the analgesic effect of intra-LC met-enkephalin microinjection. Pharmacol Biochem Behav. 2015;136:102-6 pubmed publisher
    ..Among the two types of orexin receptors (OX1R and OX2R), OX1R is highly expressed in LC neurons...
  58. Czerwińska J, Chojnowska K, Kaminski T, Bogacka I, Smolinska N, Kaminska B. Orexin receptor expression in the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes of free-living European beavers (Castor fiber L.) in different periods of the reproductive cycle. Gen Comp Endocrinol. 2017;240:103-113 pubmed publisher
    ..acting via two G protein-coupled receptors in mammals: orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R)...
  59. Zhang G, Wu X, Xu G, Weng S, Yang X, Zhong Y. Orexin-B modulates synaptic transmission of rod bipolar cells in rat retina. Neuropharmacology. 2018;133:38-50 pubmed publisher
    ..The orexin-B-induced potentiation of RBC activity may improve visual acuity and contrast sensitivity of the animal during the dark period (wake phase). ..
  60. Rashidy Pour A, Moradi M, Fatahi Z, Haghparast A, Haghparast A. Role of intra-hippocampal orexin 1 and orexin 2 receptors in conditioned place preference induced by chemical stimulation of the lateral hypothalamus. Behav Brain Res. 2015;279:106-11 pubmed publisher
    ..In this study, we assessed the role of orexin 1 (OX1r) and orexin2 (OX2r) receptors in the CA1 on the development of LH stimulation-induced conditioned place preference (CPP)...
  61. Prince C, Rau A, Yorgason J, España R. Hypocretin/Orexin regulation of dopamine signaling and cocaine self-administration is mediated predominantly by hypocretin receptor 1. ACS Chem Neurosci. 2015;6:138-46 pubmed publisher
    ..When considered with the existing literature, these data support the hypothesis that hypocretins exert a permissive influence on dopamine signaling and motivated behavior via preferential actions on hypocretin receptor 1. ..
  62. Gotter A, Forman M, Harrell C, Stevens J, Svetnik V, Yee K, et al. Orexin 2 Receptor Antagonism is Sufficient to Promote NREM and REM Sleep from Mouse to Man. Sci Rep. 2016;6:27147 pubmed publisher
    Orexin neuropeptides regulate sleep/wake through orexin receptors (OX1R, OX2R); OX2R is the predominant mediator of arousal promotion...
  63. Pruszynska Oszmalek E, Kolodziejski P, Kaczmarek P, Sassek M, Szczepankiewicz D, Mikula R, et al. Orexin A but not orexin B regulates lipid metabolism and leptin secretion in isolated porcine adipocytes. Domest Anim Endocrinol. 2018;63:59-68 pubmed publisher
    ..The action of orexins should be further explored to better understand their role in the regulation of adiposity in pigs. ..
  64. Lyons D, Hellysaz A, Ammari R, Broberger C. Hypocretin/Orexin Peptides Excite Rat Neuroendocrine Dopamine Neurons through Orexin 2 Receptor-Mediated Activation of a Mixed Cation Current. Sci Rep. 2017;7:41535 pubmed publisher
    ..it was blocked by 2-APB and was diminished by removal of extracellular Na+), and was a consequence of OX2R receptor activation (as it was blocked by the OX2R receptor antagonist TCS OX2 29, but not the OX1R receptor ..
  65. Gonzalez B, Jayanthi S, Gomez N, Torres O, Sosa M, Bernardi A, et al. Repeated methamphetamine and modafinil induce differential cognitive effects and specific histone acetylation and DNA methylation profiles in the mouse medial prefrontal cortex. Prog Neuropsychopharmacol Biol Psychiatry. 2018;82:1-11 pubmed publisher
    ..The lack of similar epigenetic effects of chronic modafinil administration supports this notion. ..
  66. Ikeno T, Yan L. A comparison of the orexin receptor distribution in the brain between diurnal Nile grass rats (Arvicanthis niloticus) and nocturnal mice (Mus musculus). Brain Res. 2018;1690:89-95 pubmed publisher
    The neuropeptide orexin/hypocretin regulates a wide range of behaviors and physiology through its receptors OX1R and OX2R, or HCRTR-1 and HCRTR-2...
  67. Zhang X, Zhu J, Geng W, Zhao S, Jiang C, Cai S, et al. Electroacupuncture at Feishu (BL13) and Zusanli (ST36) down-regulates the expression of orexins and their receptors in rats with chronic obstructive pulmonary disease. J Integr Med. 2014;12:417-24 pubmed publisher
    ..Orexin A, but not orexinB, levels in lung tissue also decreased (P<0.01), as did mRNA expression of OX1R and OX2R in lung tissue (P<0.05 and P<0.01, respectively). Receptor IODs were also reduced after EA treatment (P<0...
  68. Baccari M. Orexins and gastrointestinal functions. Curr Protein Pept Sci. 2010;11:148-55 pubmed
    ..have been shown to be widely distributed: both OXA and OXB act through two subtypes of receptors (OX1R and OX2R) that belong to the G protein-coupled superfamily of receptors...
  69. Arzhang A, Elahdadi Salmani M, Lashkarbolouki T, Goudarzi I. Posterior hypothalamus glutamate infusion decreases pentylenetetrazol-induced seizures of male rats through hippocampal histamine increase. Pharmacol Biochem Behav. 2017;158:7-13 pubmed publisher
    ..b>OX2R antagonist (TCS OX2 29, 40nmol/1?l, intra-PH), AMPA/Kainate receptor antagonist (CNQX, 3mM, intra-PH) and glutamate ..
  70. Alcaraz Iborra M, Navarrete F, Rodríguez Ortega E, De la Fuente L, Manzanares J, Cubero I. Different Molecular/Behavioral Endophenotypes in C57BL/6J Mice Predict the Impact of OX1 Receptor Blockade on Binge-Like Ethanol Intake. Front Behav Neurosci. 2017;11:186 pubmed publisher
    ..and sensitivity to the reinforcing properties of EtOH, and basal mRNA expression of the OX1/OX2 receptors (OX1r/OX2r) within the prefrontal cortex (PFC) and the nucleus accumbens (NAcc)...
  71. Zhang L, Hernandez V, Swinny J, Verma A, Giesecke T, Emery A, et al. A GABAergic cell type in the lateral habenula links hypothalamic homeostatic and midbrain motivation circuits with sex steroid signaling. Transl Psychiatry. 2018;8:50 pubmed publisher
  72. Liu F, Weng S, Yang X, Zhong Y. Orexin-A potentiates L-type calcium/barium currents in rat retinal ganglion cells. Neuroscience. 2015;305:225-37 pubmed publisher
    ..via the activation of two subtypes of G-protein-coupled receptors: orexin 1 and orexin 2 receptors (OX1R and OX2R)...
  73. Sadeghzadeh F, Namvar P, Naghavi F, Haghparast A. Differential effects of intra-accumbal orexin-1 and -2 receptor antagonists on the expression and extinction of morphine-induced conditioned place preference in rats. Pharmacol Biochem Behav. 2016;142:8-14 pubmed publisher
    ..administration of SB334867 as an orexin-1 receptor (OX1R) antagonist and TCS OX2 29 as an orexin-2 receptor (OX2R) antagonist in the expression and maintenance of morphine-induced conditioned place preference (CPP) in rats...
  74. Fatemi I, Shamsizadeh A, Roohbakhsh A, Ayoobi F, Sanati M, Motevalian M. Increase in mRNA Level of Orexin1 and 2 Receptors Following Induction of Experimental Autoimmune Encephalomyelitis in Mice. Iran J Allergy Asthma Immunol. 2016;15:20-6 pubmed
    ..Then, the expression profiles of prepro-orexin, orexin 1 receptors (OX1R) and orexin 2 receptors (OX2R) in hypothalamic region were assessed using real-time PCR method...
  75. Liguori G, Tafuri S, Miyoshi C, Yanagisawa M, Squillacioti C, De Pasquale V, et al. Localization of orexin B and orexin-2 receptor in the rat epididymis. Acta Histochem. 2018;120:292-297 pubmed publisher
    ..Both OXA and OXB peptides bind to two G-coupled receptors, orexin-1 (OX1R) and orexin-2 (OX2R) receptor, though with different binding affinity...
  76. Liguori G, Squillacioti C, Assisi L, Pelagalli A, Vittoria A, Costagliola A, et al. Potential role of orexin A binding the receptor 1 for orexins in normal and cryptorchid dogs. BMC Vet Res. 2018;14:55 pubmed publisher
    ..These substances bind two types of G-coupled receptors called receptor 1 (OX1R) and 2 (OX2R) for orexins. OX1R is specific to OxA while OX2R binds the two peptides with equal affinity...
  77. Yazdi F, Jahangirvand M, Pirasteh A, Moradi M, Haghparast A. Functional interaction between OX2 and CB1 receptors in the ventral tegmental area and the nucleus accumbens in response to place preference induced by chemical stimulation of the lateral hypothalamus. Pharmacol Biochem Behav. 2015;139:39-46 pubmed publisher
    ..In this study, the authors tried to clarify the role of orexin-2 receptor (OX2r) within the VTA and NAc in the development of reward-related behaviors after chemical stimulation of the LH and ..
  78. Schwartz M, Nguyen A, Warrier D, Palmerston J, Thomas A, Morairty S, et al. Locus Coeruleus and Tuberomammillary Nuclei Ablations Attenuate Hypocretin/Orexin Antagonist-Mediated REM Sleep. Eneuro. 2016;3: pubmed publisher
  79. D angelo L, Castaldo L, De Girolamo P, Lucini C, Paolucci M, Pelagalli A, et al. Orexins and receptor OX2R in the gastroenteric apparatus of two teleostean species: Dicentrarchus labrax and Carassius auratus. Anat Rec (Hoboken). 2016;299:1121-9 pubmed publisher
    Orexin A and B peptides and the receptor OX2R were studied in sea bass and goldfish gastroenteric tract by immunoblotting combined with densitometric analysis using NIH Image J software and immunohistochemical techniques...
  80. McDonald T, Liang H, Sanoja R, Gotter A, Kuduk S, Coleman P, et al. Pharmacological evaluation of orexin receptor antagonists in preclinical animal models of pain. J Neurogenet. 2016;30:32-41 pubmed publisher
    ..in the formalin model were also observed in orexin 1 receptor (OX1R) knockout mice, but not orexin 2 receptor (OX2R) or OX1R/OX2R double knockout mice...
  81. Matzeu A, Kerr T, Weiss F, Martin Fardon R. Orexin-A/Hypocretin-1 Mediates Cocaine-Seeking Behavior in the Posterior Paraventricular Nucleus of the Thalamus via Orexin/Hypocretin Receptor-2. J Pharmacol Exp Ther. 2016;359:273-279 pubmed
  82. Rainero I, Rubino E, Valfrè W, Gallone S, De Martino P, Zampella E, et al. Association between the G1246A polymorphism of the hypocretin receptor 2 gene and cluster headache: a meta-analysis. J Headache Pain. 2007;8:152-6 pubmed
    ..75, CI 95% 1.37-2.25; RE OR 1.69, CI 95% 1.11-2.58). Our data confirm that the G1246A polymorphism of the HCRTR2 gene may modulate the genetic risk for CH. ..
  83. Annerbrink K, Westberg L, Olsson M, Andersch S, Sjödin I, Holm G, et al. Panic disorder is associated with the Val308Iso polymorphism in the hypocretin receptor gene. Psychiatr Genet. 2011;21:85-9 pubmed publisher
    ..The results should be regarded as preliminary until replicated in an independent sample. This indicates that further research on the possible role of orexin in panic disorder may prove rewarding. ..
  84. Yazdi F, Jahangirvand M, Ezzatpanah S, Haghparast A. Role of orexin-2 receptors in the nucleus accumbens in antinociception induced by carbachol stimulation of the lateral hypothalamus in formalin test. Behav Pharmacol. 2016;27:431-8 pubmed publisher
    ..A volume of 0.5 μl of 10, 20, and 40 nmol/l solutions of TCS OX2 29, an OX2r antagonist, were unilaterally microinjected into the NAc 5 min before an intra-LH carbachol microinjection (..
  85. Fan Z, Hou L, Wan D, Ao R, Zhao D, Yu S. Genetic association of HCRTR2, ADH4 and CLOCK genes with cluster headache: a Chinese population-based case-control study. J Headache Pain. 2018;19:1 pubmed publisher
    ..Association between HCRTR2, ADH4,CLOCK gene polymorphisms and CH was not significant in the present study, however, haplotype analysis indicated H1-GTGGGG was linked to a reduced CH risk. ..
  86. Beig M, Horiuchi J, Dampney R, Carrive P. Both Ox1R and Ox2R orexin receptors contribute to the cardiorespiratory response evoked from the perifornical hypothalamus. Clin Exp Pharmacol Physiol. 2015;42:1059-67 pubmed publisher
    ..nearly half or more by systemic Almorexant, a dual receptor antagonist of the two known orexin receptors, Ox1R and Ox2R. It is not clear if these reductions result from the blockade of one receptor or both...
  87. Nagahara T, Saitoh T, Kutsumura N, Irukayama Tomobe Y, Ogawa Y, Kuroda D, et al. Design and Synthesis of Non-Peptide, Selective Orexin Receptor 2 Agonists. J Med Chem. 2015;58:7931-7 pubmed publisher
    ..that regulate sleep/wakefulness, acting on two G-protein-coupled receptors, orexin receptors 1 (OX1R) and 2 (OX2R)...
  88. Du M, Hunt N, Waters K, Machaalani R. Cumulative effects of repetitive intermittent hypercapnic hypoxia on orexin in the developing piglet hypothalamus. Int J Dev Neurosci. 2016;48:1-8 pubmed publisher
    Orexin neuropeptides (OxA and OxB) and their receptors (OX1R and OX2R) are involved in maintenance of sleep and wakefulness, and are regulated by various environmental stimuli...
  89. Lu G, Lee C, Chiou L. Orexin A induces bidirectional modulation of synaptic plasticity: Inhibiting long-term potentiation and preventing depotentiation. Neuropharmacology. 2016;107:168-180 pubmed publisher
    The orexin system consists of two peptides, orexin A and B and two receptors, OX1R and OX2R. It is implicated in learning and memory regulation while controversy remains on its role in modulating hippocampal synaptic plasticity in vivo ..
  90. Sadeghi B, Ezzatpanah S, Haghparast A. Effects of dorsal hippocampal orexin-2 receptor antagonism on the acquisition, expression, and extinction of morphine-induced place preference in rats. Psychopharmacology (Berl). 2016;233:2329-41 pubmed publisher
    ..Here, we investigated the effect of intrahippocampal CA1 administration of orexin-2 receptor (OX2r) antagonist on the acquisition, expression, and extinction of morphine-induced place preference in rats...
  91. Karteris E, Chen J, Randeva H. Expression of human prepro-orexin and signaling characteristics of orexin receptors in the male reproductive system. J Clin Endocrinol Metab. 2004;89:1957-62 pubmed
    ..actions by binding and activating two types of G protein-coupled receptors, OR-1 receptor (OX1R) and OR-2 receptor (OX2R)...
  92. Farahimanesh S, Zarrabian S, Haghparast A. Role of orexin receptors in the ventral tegmental area on acquisition and expression of morphine-induced conditioned place preference in the rats. Neuropeptides. 2017;66:45-51 pubmed publisher
    ..a selective orexin-1 receptor (OX1R) antagonist, or TCS-OX2-29 (1, 5 and 25nM), a selective orexin-2 receptor (OX2R) antagonist...