Gene Symbol: orexin
Description: hypocretin neuropeptide precursor
Alias: NRCLP1, PPOX, orexin, hypocretin (orexin) neuropeptide, prepro-orexin
Species: human
Products:     orexin

Top Publications

  1. 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
    ..These peptides, termed orexin-A and -B, have no significant structural similarities to known families of regulatory peptides...
  2. 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;92:1 page following 696 pubmed
  3. Sakurai T, Moriguchi T, Furuya K, Kajiwara N, Nakamura T, Yanagisawa M, et al. Structure and function of human prepro-orexin gene. J Biol Chem. 1999;274:17771-6 pubmed
    b>Orexin-A and -B are recently identified potent orexigenic peptides that are derived from the same precursor peptide and are highly specifically localized in neurons located in the lateral hypothalamic area, a region classically implicated ..
  4. Tsujino N, Sakurai T. Orexin/hypocretin: a neuropeptide at the interface of sleep, energy homeostasis, and reward system. Pharmacol Rev. 2009;61:162-76 pubmed publisher
    Recent studies have implicated the orexin system as a critical regulator of sleep/wake states as well as feeding behavior and reward processes...
  5. 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. ..
  6. Fronczek R, van Geest S, Frolich M, Overeem S, Roelandse F, Lammers G, et al. Hypocretin (orexin) loss in Alzheimer's disease. Neurobiol Aging. 2012;33:1642-50 pubmed publisher
    ..In this study, we assessed whether the neurodegenerative process of AD also affects hypothalamic hypocretin/orexin neurons...
  7. Salomon R, Ripley B, Kennedy J, Johnson B, Schmidt D, Zeitzer J, et al. Diurnal variation of cerebrospinal fluid hypocretin-1 (Orexin-A) levels in control and depressed subjects. Biol Psychiatry. 2003;54:96-104 pubmed
    ..The finding that sertraline but not bupropion slightly decreased cerebrospinal fluid hypocretin-1 indicates a serotoninergic influence on hypocretin tone. ..
  8. Baranowska B, Wolinska Witort E, Martynska L, Martyńska M, Chmielowska M, Baranowska Bik A. Plasma orexin A, orexin B, leptin, neuropeptide Y (NPY) and insulin in obese women. Neuro Endocrinol Lett. 2005;26:293-6 pubmed
    ..Material consisted of 36 obese women and 16 lean women. Plasma orexin A, orexin B, neuropeptide Y (NPY), leptin, insulin concentrations were measured with RIA methods...
  9. LESSIG S, Ubhi K, Galasko D, Adame A, Pham E, Remidios K, et al. Reduced hypocretin (orexin) levels in dementia with Lewy bodies. Neuroreport. 2010;21:756-60 pubmed publisher
    ..Reduced hypocretin (orexin) levels are reported in Parkinson's disease and sleep disorders, including narcolepsy; however, its levels in ..

More Information

Publications138 found, 100 shown here

  1. Peyron C, Faraco J, Rogers W, Ripley B, Overeem S, Charnay Y, et al. A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat Med. 2000;6:991-7 pubmed
    ..Although hypocretin loci do not contribute significantly to genetic predisposition, most cases of human narcolepsy are associated with a deficient hypocretin system. ..
  2. Finley J. Cellular stress and AMPK links metformin and diverse compounds with accelerated emergence from anesthesia and potential recovery from disorders of consciousness. Med Hypotheses. 2019;124:42-52 pubmed publisher
    ..circuits that promote wakefulness, arousal, and consciousness activates AMPK, including acetylcholine, histamine, orexin-A, dopamine, and norepinephrine...
  3. Chrościcki P, Usarek M, Bryla J. [The role of biological clock in glucose homeostasis]. Postepy Hig Med Dosw (Online). 2013;67:569-83 pubmed publisher
    ..Thus, glucose production and utilization are synchronized in time. The hypothalamic excited orexin neurons control energy balance of organism and modulate the glucose production and utilization...
  4. Benarroch E. Control of the cardiovascular and respiratory systems during sleep. Auton Neurosci. 2019;218:54-63 pubmed publisher
    ..GABA) and are modulated in a state-dependent manner by inputs from cholinergic, monoaminergic, and hypothalamic orexin/hypocretin and melanin-concentrating hormone (MCH) neurons...
  5. Hassani O, Krause M, Mainville L, CORDOVA C, Jones B. Orexin Neurons Respond Differentially to Auditory Cues Associated with Appetitive versus Aversive Outcomes. J Neurosci. 2016;36:1747-57 pubmed publisher
    b>Orexin (Orx) neurons are known to be involved in the promotion and maintenance of waking because they discharge in association with cortical activation and muscle tone during waking and because, in their absence, waking with muscle tone ..
  6. Semmens D, Mirabeau O, Moghul I, Pancholi M, Wurm Y, Elphick M. Transcriptomic identification of starfish neuropeptide precursors yields new insights into neuropeptide evolution. Open Biol. 2016;6:150224 pubmed publisher
    ..hormone-type, thyrotropin-releasing hormone-type, calcitonin-type, cholecystokinin/gastrin-type, orexin-type, luqin-type, pedal peptide/orcokinin-type, glycoprotein hormone-type, bursicon-type, relaxin-type and insulin-..
  7. 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
    b>Orexin-A and -B are hypothalamic neuropeptides of 33 and 28-amino acids, which regulate many homeostatic systems including sleep/wakefulness states, energy balance, energy homeostasis, reward seeking and drug addiction...
  8. Sadam H, Pihlak A, Kivil A, Pihelgas S, Jaago M, Adler P, et al. Prostaglandin D2 Receptor DP1 Antibodies Predict Vaccine-induced and Spontaneous Narcolepsy Type 1: Large-scale Study of Antibody Profiling. EBioMedicine. 2018;29:47-59 pubmed publisher
    Neuropathological findings support an autoimmune etiology as an underlying factor for loss of orexin-producing neurons in spontaneous narcolepsy type 1 (narcolepsy with cataplexy; sNT1) as well as in Pandemrix influenza vaccine-induced ..
  9. Morello G, Imperatore R, Palomba L, Finelli C, Labruna G, Pasanisi F, et al. Orexin-A represses satiety-inducing POMC neurons and contributes to obesity via stimulation of endocannabinoid signaling. Proc Natl Acad Sci U S A. 2016;113:4759-64 pubmed publisher
    ..POMC neurons receive orexin-A (OX-A)-expressing inputs and express both OX-A receptor type 1 (OX-1R) and cannabinoid receptor type 1 (CB1R) on ..
  10. Meletti S, Vaudano A, Pizza F, Ruggieri A, Vandi S, Teggi A, et al. The Brain Correlates of Laugh and Cataplexy in Childhood Narcolepsy. J Neurosci. 2015;35:11583-94 pubmed publisher
    ..In narcolepsy caused by hypocretin/orexin deficiency, cataplexy is associated with a marked increase in neural activity in the amygdala, the nucleus ..
  11. Horiuchi M, Nakakuma M, Arimura E, Ushikai M, Yoshida G. [Experimental Approach to Analysis of the Relationship between Food Environments and Lifestyle-Related Diseases, Including Cardiac Hypertrophy, Fatty Liver, and Fatigue Symptoms]. Nihon Eiseigaku Zasshi. 2015;70:110-4 pubmed publisher
    ..In addition, the mice showed disturbance of orexin neuron activity related to the sleep-arousal system, which is involved in fatigue symptoms under fasting condition,..
  12. Del Cid Pellitero E, Garzón M. Hypocretin1/orexinA-immunoreactive axons form few synaptic contacts on rat ventral tegmental area neurons that project to the medial prefrontal cortex. BMC Neurosci. 2014;15:105 pubmed publisher
    ..Our observation of Hcrt1/OxA targeting of mesocortical neurons supports Hcrt1/OxA wakefulness enhancement in the VTA and could help explain the characteristic hypersomnia present in narcoleptic patients. ..
  13. Liu J, Bello N, Pang Z. Presynaptic Regulation of Leptin in a Defined Lateral Hypothalamus-Ventral Tegmental Area Neurocircuitry Depends on Energy State. J Neurosci. 2017;37:11854-11866 pubmed publisher
    ..we found that leptin reduces excitatory synaptic strength onto both melanin-concentrating hormone- and orexin-expressing neurons projecting from the LHA to the ventral tegmental area (VTA), which may affect dopamine ..
  14. Hunt N, Waters K, Machaalani R. Promotion of the Unfolding Protein Response in Orexin/Dynorphin Neurons in Sudden Infant Death Syndrome (SIDS): Elevated pPERK and ATF4 Expression. Mol Neurobiol. 2017;54:7171-7185 pubmed publisher
    We previously demonstrated that sudden infant death syndrome (SIDS) infants have decreased orexin immunoreactivity within the hypothalamus and pons compared to non-SIDS infants...
  15. Janockova J, Dolezal R, Nepovimova E, Kobrlova T, Benkova M, Kuca K, et al. Investigation of New Orexin 2 Receptor Modulators Using In Silico and In Vitro Methods. Molecules. 2018;23: pubmed publisher
    The neuropeptides, orexin A and orexin B (also known as hypocretins), are produced in hypothalamic neurons and belong to ligands for orphan G protein-coupled receptors...
  16. Butt Z, Hackett J, Volkoff H. Irisin in goldfish (Carassius auratus): Effects of irisin injections on feeding behavior and expression of appetite regulators, uncoupling proteins and lipoprotein lipase, and fasting-induced changes in FNDC5 expression. Peptides. 2017;90:27-36 pubmed publisher
    ..of appetite regulators (cocaine and amphetamine regulated transcript CART, agouti related protein AgRP, orexin), UCPs and lipoprotein lipase LPL and brain factors (brain-derived neurotrophic factor , BDNF and tyrosine ..
  17. Mohammadi S, Dolatshahi M, Zare Shahabadi A, Rahmani F. Untangling Narcolepsy and Diabetes: Pathomechanisms with Eyes on Therapeutic Options. Brain Res. 2019;: pubmed publisher
    ..b>Orexin deficiency, is associated with increased food intake and reduced basal metabolic rate (BMR) both leading to ..
  18. Buture A, Boland J, Dikomitis L, Ahmed F. Update on the pathophysiology of cluster headache: imaging and neuropeptide studies. J Pain Res. 2019;12:269-281 pubmed publisher
    ..tractography, connectivity, cerebral networks, neuromodulation, central modulation, deep brain stimulation, orexin-A, orexin-B, tract-based spatial statistics, single-photon emission computer tomography studies, positron-emission ..
  19. Mandic S, Volkoff H. The effects of fasting and appetite regulators on catecholamine and serotonin synthesis pathways in goldfish (Carassius auratus). Comp Biochem Physiol A Mol Integr Physiol. 2018;223:1-9 pubmed publisher
    ..monoaminergic pathways and appetite-regulating hormones, we examined the effects of intraperitoneal injections of orexin, CCK and irisin on the brain and intestine gene expression of these enzymes...
  20. Singh R, Bansal Y, Medhi B, Kuhad A. Antipsychotics-induced metabolic alterations: Recounting the mechanistic insights, therapeutic targets and pharmacological alternatives. Eur J Pharmacol. 2019;844:231-240 pubmed publisher
    ..is linked to altered expression of uncoupling proteins (UCP-1) in brown adipose tissue and reduced hypothalamic orexin expressions are emerging insights...
  21. Mahoney C, Agostinelli L, Brooks J, Lowell B, Scammell T. GABAergic Neurons of the Central Amygdala Promote Cataplexy. J Neurosci. 2017;37:3995-4006 pubmed publisher
    ..This condition is caused by a lack of orexin (hypocretin) signaling, but little is known about the neural mechanisms that mediate cataplexy...
  22. Bernard Valnet R, Yshii L, Quériault C, Nguyen X, Arthaud S, Rodrigues M, et al. CD8 T cell-mediated killing of orexinergic neurons induces a narcolepsy-like phenotype in mice. Proc Natl Acad Sci U S A. 2016;113:10956-61 pubmed publisher
    ..Here, we sought to generate a mouse model that allows deciphering of the immune mechanisms leading to orexin(+) neuron loss and narcolepsy development...
  23. Barateau L, Lopez R, Dauvilliers Y. Management of Narcolepsy. Curr Treat Options Neurol. 2016;18:43 pubmed publisher
    ..Immune-based therapies are other possibilities in NT1, at disease onset, with already some successful attempts to slow down or stop the autoimmune process. ..
  24. Silvani A, Bastianini S, Berteotti C, Cenacchi G, Leone O, Lo Martire V, et al. Sleep and cardiovascular phenotype in middle-aged hypocretin-deficient narcoleptic mice. J Sleep Res. 2014;23:98-106 pubmed publisher
    Narcolepsy with cataplexy (NC) is a lifelong disorder caused by loss of hypothalamic hypocretin/orexin (HCRT) neurones, often starting in childhood...
  25. Szabo S, Thorpy M, Mayer G, Peever J, Kilduff T. Neurobiological and immunogenetic aspects of narcolepsy: Implications for pharmacotherapy. Sleep Med Rev. 2019;43:23-36 pubmed publisher
    ..EDS) and cataplexy are common symptoms of narcolepsy, a sleep disorder associated with the loss of hypocretin/orexin (Hcrt) neurons...
  26. Sachidanandan D, Reddy H, Mani A, Hyde G, Bera A. The Neuropeptide Orexin-A Inhibits the GABAA Receptor by PKC and Ca2+/CaMKII-Dependent Phosphorylation of Its ?1 Subunit. J Mol Neurosci. 2017;61:459-467 pubmed publisher
    b>Orexin-A and orexin-B (Ox-A, Ox-B) are neuropeptides produced by a small number of neurons that originate in the hypothalamus and project widely in the brain...
  27. Celik O, Aydin S, Celik N, Yilmaz M. Peptides: Basic determinants of reproductive functions. Peptides. 2015;72:34-43 pubmed publisher
    ..Particular attention will be paid to summarize the participation of leptin, kisspeptin, ghrelin, NPY, orexin, urocortin, VIP, insulin, galanin, galanin like peptide, oxytocin, agouti gene-related peptide, and POMC neurons ..
  28. Agostinelli L, Ferrari L, Mahoney C, Mochizuki T, Lowell B, Arrigoni E, et al. Descending projections from the basal forebrain to the orexin neurons in mice. J Comp Neurol. 2017;525:1668-1684 pubmed publisher
    The orexin (hypocretin) neurons play an essential role in promoting arousal, and loss of the orexin neurons results in narcolepsy, a condition characterized by chronic sleepiness and cataplexy...
  29. Irani S, Pettingill P, Kleopa K, Schiza N, Waters P, Mazia C, et al. Morvan syndrome: clinical and serological observations in 29 cases. Ann Neurol. 2012;72:241-55 pubmed publisher
    ..commercial antibodies to LGI1 bound to neuronal cell bodies including the antidiuretic hormone-secreting and orexin-secreting hypothalamic neurons, whereas CASPR2 commercial antibodies bound more often to the neuropil...
  30. Tarnawski A, Ahluwalia A. Molecular mechanisms of epithelial regeneration and neovascularization during healing of gastric and esophageal ulcers. Curr Med Chem. 2012;19:16-27 pubmed
    ..by the cytokines and growth factors, GI hormones including gastrin, CCK, and orexigenic peptides such as ghrelin, orexin-A and obestatin as well as Cox2 generated prostaglandins...
  31. Dye T, Gurbani N, Simakajornboon N. Epidemiology and Pathophysiology of Childhood Narcolepsy. Paediatr Respir Rev. 2018;25:14-18 pubmed publisher
    ..Narcolepsy type I or Narcolepsy with cataplexy is caused by the loss of hypocretin or orexin neurons. Narcolepsy type II or narcolepsy without cataplexy has normal hypocretin and the etiology is unknown...
  32. Baladi M, Forster M, Gatch M, Mailman R, Hyman D, Carter L, et al. Characterization of the Neurochemical and Behavioral Effects of Solriamfetol (JZP-110), a Selective Dopamine and Norepinephrine Reuptake Inhibitor. J Pharmacol Exp Ther. 2018;366:367-376 pubmed publisher
    ..owing to activity at DA and NE transporters rather than other neurotransmitter systems, such as histamine or orexin. The dual activity of solriamfetol at DA and NE transporters and the lack of significant monoamine-releasing ..
  33. Abad V, Guilleminault C. Insomnia in Elderly Patients: Recommendations for Pharmacological Management. Drugs Aging. 2018;35:791-817 pubmed publisher
    ..Current drugs for insomnia fall into different classes: orexin agonists, histamine receptor antagonists, non-benzodiazepine gamma aminobutyric acid receptor agonists, and ..
  34. Naganuma F, Bandaru S, Absi G, Mahoney C, Scammell T, Vetrivelan R. Melanin-concentrating hormone neurons contribute to dysregulation of rapid eye movement sleep in narcolepsy. Neurobiol Dis. 2018;120:12-20 pubmed publisher
    ..Narcolepsy with cataplexy is caused by selective loss of the orexin neurons, and the MCH neurons appear unaffected...
  35. Wagner L, Kaestner F, Wolf R, Stiller H, Heiser U, Manhart S, et al. Identifying neuropeptide Y (NPY) as the main stress-related substrate of dipeptidyl peptidase 4 (DPP4) in blood circulation. Neuropeptides. 2016;57:21-34 pubmed publisher
    ..modification of DPP4-isoforms and degradation of NPY, Peptide YY (PYY), Galanin-like peptide (GALP), Orexin B (OrxB), OrxA, pituitary adenylate cyclase-activating polypeptide (PACAP) and substance P (SP) were studied in ..
  36. James M, Campbell E, Dayas C. Role of the Orexin/Hypocretin System in Stress-Related Psychiatric Disorders. Curr Top Behav Neurosci. 2017;33:197-219 pubmed publisher
    ..Acute stressors engage orexin neurons via direct projections from stress-sensitive brain regions...
  37. Meerabux J, Iwayama Y, Sakurai T, Ohba H, Toyota T, Yamada K, et al. Association of an orexin 1 receptor 408Val variant with polydipsia-hyponatremia in schizophrenic subjects. Biol Psychiatry. 2005;58:401-7 pubmed
    ..Both angiotensin-converting enzyme (ACE) and orexin (hypocretin) signaling can modulate drinking behavior through interactions with the dopaminergic system...
  38. von der Goltz C, Koopmann A, Dinter C, Richter A, Grosshans M, Fink T, et al. Involvement of orexin in the regulation of stress, depression and reward in alcohol dependence. Horm Behav. 2011;60:644-50 pubmed publisher
    ..Moreover, the effects on global distress indices as well as the earlier studied effects on reinstatement of drug seeking behaviors may point on an involvement of ORX in impaired brain stress systems...
  39. Yilmaz E, Celik O, Celik N, Celik E, Türkçüoğlu I, Simsek Y, et al. Maternal and fetal serum orexin-A levels in gestational diabetes mellitus. J Obstet Gynaecol Res. 2013;39:139-45 pubmed publisher
    Evidence suggests that orexin regulates food consumption, glucose metabolism and insulin secretion. Orexin may have a role in the pathogenesis of type II diabetes mellitus, however its role in gestational diabetes mellitus is not known...
  40. Johansson P, Almqvist E, Wallin A, Johansson J, Andreasson U, Blennow K, et al. Cerebrospinal fluid substance P concentrations are elevated in patients with Alzheimer's disease. Neurosci Lett. 2015;609:58-62 pubmed publisher
    The neuropeptides substance P, orexin A (hypocretin-1) and neurotensin are signaling molecules that influence brain activity...
  41. Zizza M, Canonaco M, Facciolo R. Orexin-A Rescues Chronic Copper-Dependent Behavioral and HSP90 Transcriptional Alterations in the Ornate Wrasse Brain. Neurotox Res. 2017;31:578-589 pubmed publisher
    Recently, orexin (ORX)ergic system has gained great attention for its major neuroregulatory role on fish motor, circadian, feeding activities and above all during water toxic conditions...
  42. Zink A, Bunney P, Holm A, Billington C, Kotz C. Neuromodulation of orexin neurons reduces diet-induced adiposity. Int J Obes (Lond). 2018;42:737-745 pubmed publisher
    Low levels of orexin are associated with obesity and reduced physical activity in humans and animals...
  43. Santiago J, Otto M, Kern W, Baier P, Hallschmid M. Relationship between cerebrospinal fluid concentrations of orexin A/hypocretin-1 and body composition in humans. Peptides. 2018;102:26-30 pubmed publisher
    The hypothalamic neuropeptide orexin A (hypocretin-1) is a key signal in sleep/wake regulation and promotes food intake...
  44. Atkin T, Comai S, Gobbi G. Drugs for Insomnia beyond Benzodiazepines: Pharmacology, Clinical Applications, and Discovery. Pharmacol Rev. 2018;70:197-245 pubmed publisher
    ..the melatonergic agonist drugs, agomelatine, prolonged-release melatonin, ramelteon, and tasimelteon; the dual orexin receptor antagonist suvorexant; the modulators of the α2δ subunit of voltage-sensitive ..
  45. Papuc E, Stelmasiak Z, Zbigniew S, Grieb P, Paweł G, Rejdak K, et al. CSF hypocretin-1 concentrations correlate with the level of fatigue in multiple sclerosis patients. Neurosci Lett. 2010;474:9-12 pubmed publisher
  46. Kukkonen J. OX2 orexin/hypocretin receptor signal transduction in recombinant Chinese hamster ovary cells. Cell Signal. 2016;28:51-60 pubmed publisher
    There are two subtypes of orexin receptors, OX1 and OX2. Signalling pathways have been mapped in much higher detail for OX1 receptors than OX2 receptors...
  47. Black S, Yamanaka A, Kilduff T. Challenges in the development of therapeutics for narcolepsy. Prog Neurobiol. 2017;152:89-113 pubmed publisher
    ..Disruption of neurotransmission through the hypocretin/orexin (Hcrt) system, usually by degeneration of the HCRT-producing neurons in the posterior hypothalamus, results in ..
  48. Dai Y, Lee Y, Chen J, Lin Y, Hwang L. Expression of the M3 Muscarinic Receptor on Orexin Neurons that Project to the Rostral Ventrolateral Medulla. Anat Rec (Hoboken). 2016;299:660-8 pubmed publisher
    ..Projections from hypothalamic orexin neurons to the rostral ventrolateral medulla (RVLM) are involved in sympatho-excitation of the cardiovascular ..
  49. Ozsoy S, Olguner Eker O, Abdulrezzak U, Esel E. Relationship between orexin A and childhood maltreatment in female patients with depression and anxiety. Soc Neurosci. 2017;12:330-336 pubmed publisher
    ..This study aimed to investigate the relationship between childhood maltreatment and orexin A levels in patients with depression and anxiety...
  50. 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
    The neuropeptides orexin-A and orexin-B are widely expressed in the vertebrate retina; however, their role in visual function is unclear...
  51. Gencik M, Dahmen N, Wieczorek S, Kasten M, Bierbrauer J, Anghelescu I, et al. A prepro-orexin gene polymorphism is associated with narcolepsy. Neurology. 2001;56:115-7 pubmed
    The orexin (hypocretin) neurotransmitter system was recently shown to be directly involved in the pathogenesis of narcolepsy in two animal models. Furthermore, decreased levels of orexin A in the CSF were shown in narcoleptic patients...
  52. Andersson H, Björnström K, Eintrei C, Sundqvist T. Orexin a phosphorylates the γ-Aminobutyric acid type A receptor β2 subunit on a serine residue and changes the surface expression of the receptor in SH-SY5Y cells exposed to propofol. J Neurosci Res. 2015;93:1748-55 pubmed publisher
    ..The awakening peptide orexin A (OA) inhibits this retraction via phospholipase D (PLD) and protein kinase CÉ› (PKCÉ›)...
  53. Gac L, Butterick T, Duffy C, Teske J, Perez Leighton C. Role of the non-opioid dynorphin peptide des-Tyr-dynorphin (DYN-A(2-17)) in food intake and physical activity, and its interaction with orexin-A. Peptides. 2016;76:14-8 pubmed publisher
    Food intake and physical activity are regulated by multiple neuropeptides, including orexin and dynorphin (DYN)...
  54. Federico A, Dallio M, Tolone S, Gravina A, Patrone V, Romano M, et al. Gastrointestinal Hormones, Intestinal Microbiota and Metabolic Homeostasis in Obese Patients: Effect of Bariatric Surgery. In Vivo. 2016;30:321-30 pubmed
    ..We evaluated food intake, plasma levels of peptide YY (PYY), glucagon-like peptide-1/2 (GLP-1/2), ghrelin (GHR), orexin (ORE) and cholecystokinin (CCK), body composition and fecal microbiota in 28 severely obese patients and 28 ..
  55. Volkoff H, Estevan Sabioni R, Coutinho L, Cyrino J. Appetite regulating factors in pacu (Piaractus mesopotamicus): Tissue distribution and effects of food quantity and quality on gene expression. Comp Biochem Physiol A Mol Integr Physiol. 2017;203:241-254 pubmed publisher
    ..Little is known about the endocrine regulation of feeding in this species. In this study, transcripts for orexin, cocaine and amphetamine regulated transcript (CART), cholecystokinin (CCK) and leptin were isolated in pacu...
  56. Hagar J, Macht V, Wilson S, Fadel J. Upregulation of orexin/hypocretin expression in aged rats: Effects on feeding latency and neurotransmission in the insular cortex. Neuroscience. 2017;350:124-132 pubmed publisher
    ..b>Orexin/hypocretin neurons of the hypothalamus regulate several physiological functions, including feeding, sleep and ..
  57. Sánchez García A, Cabral Pacheco G, Zomosa Signoret V, Ortiz Lopez R, Camacho A, Tabera Tarello P, et al. Modular organization of a hypocretin gene minimal promoter. Mol Med Rep. 2018;17:2263-2270 pubmed publisher
    ..There is an interest in defining the key molecular elements in orexin regulation, as these may serve to identify targets for generating novel therapies for sleep disorders, obesity and ..
  58. Briggs C, Hirasawa M, Semba K. Sleep Deprivation Distinctly Alters Glutamate Transporter 1 Apposition and Excitatory Transmission to Orexin and MCH Neurons. J Neurosci. 2018;38:2505-2518 pubmed publisher
    ..We found that SD decreased perisomatic GLT1 apposition with wake-promoting orexin neurons in the lateral hypothalamus compared with Rest...
  59. Baldo B, Kelley A. Amylin infusion into rat nucleus accumbens potently depresses motor activity and ingestive behavior. Am J Physiol Regul Integr Comp Physiol. 2001;281:R1232-42 pubmed
    ..In contrast to amylin's effects, intra-Acb shell infusions of orexin-A (50, 100, and 500 ng/side) had no effects on motor activity, feeding, or drinking...
  60. Stengel A, Karasawa H, TACHE Y. The role of brain somatostatin receptor 2 in the regulation of feeding and drinking behavior. Horm Behav. 2015;73:15-22 pubmed publisher
    ..The orexigenic response involves downstream orexin-1, neuropeptide Y1 and ? receptor signaling while the dipsogenic effect is mediated through the activation of the ..
  61. Okumura T, Nozu T, Kumei S, Takakusaki K, Miyagishi S, Ohhira M. Adenosine A1 receptors mediate the intracisternal injection of orexin-induced antinociceptive action against colonic distension in conscious rats. J Neurol Sci. 2016;362:106-10 pubmed publisher
    We have recently demonstrated that orexin acts centrally through the brain orexin 1 receptors to induce an antinociceptive action against colonic distension in conscious rats...
  62. Keefer S, Cole S, Petrovich G. Orexin/hypocretin receptor 1 signaling mediates Pavlovian cue-food conditioning and extinction. Physiol Behav. 2016;162:27-36 pubmed publisher
    Learned food cues can drive feeding in the absence of hunger, and orexin/hypocretin signaling is necessary for this type of overeating...
  63. Lopez J, Morales L, González A. Spatiotemporal Development of the Orexinergic (Hypocretinergic) System in the Central Nervous System of Xenopus laevis. Brain Behav Evol. 2016;88:127-146 pubmed
    The present immunohistochemical study represents a detailed spatiotemporal analysis of the localization of orexin-immunoreactive (OX-ir) cells and fibers throughout development in the brain of the anuran amphibian Xenopus laevis, a model ..
  64. Wu S, Sun Y, Hu Y, Zhang H, Hou L, Liu X, et al. Discovery of novel substituted octahydropyrrolo[3,4-c]pyrroles as dual orexin receptor antagonists for insomnia treatment. Bioorg Med Chem Lett. 2017;27:1458-1462 pubmed publisher
    A series of octahydropyrrolo[3,4-c]pyrroles were synthesized and evaluated by orexin 1 and 2 receptor (OX1 & 2 R) antagonists assays...
  65. Gantz S, Bean B. Cell-Autonomous Excitation of Midbrain Dopamine Neurons by Endocannabinoid-Dependent Lipid Signaling. Neuron. 2017;93:1375-1387.e2 pubmed publisher
    ..Activation of orexin, neurotensin, and metabotropic glutamate Gq/11-linked receptors mimicked the effects of exogenous 2-AG ..
  66. Kołodziejski P, Pruszyńska Oszmałek E, Korek E, Sassek M, Szczepankiewicz D, Kaczmarek P, et al. Serum levels of spexin and kisspeptin negatively correlate with obesity and insulin resistance in women. Physiol Res. 2018;67:45-56 pubmed
    ..SPX or KISS with BMI, McAuley index, QUICKI, HOMA IR, serum levels of insulin, glucagon, leptin, adiponectin, orexin-A, obestatin, ghrelin and GLP-1 were assessed...
  67. Luo G, Lin L, Jacob L, Bonvalet M, Ambati A, Plazzi G, et al. Absence of anti-hypocretin receptor 2 autoantibodies in post pandemrix narcolepsy cases. PLoS ONE. 2017;12:e0187305 pubmed publisher
    ..None of the post Pandemrix® narcolepsy cases (0 of 40 sera) was found positive with all three strategies. Anti-HCRTR2 autoantibody is not a significant biological feature of narcolepsy or of post Pandemrix® autoimmune responses. ..
  68. 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...
  69. Di Cristoforo A, Cerri M, Del Vecchio F, Hitrec T, Luppi M, Perez E, et al. Wake-sleep, thermoregulatory, and autonomic effects of cholinergic activation of the lateral hypothalamus in the rat: a pilot study. Arch Ital Biol. 2015;153:67-76 pubmed publisher
    ..the wake-promoting effects of the activation of the lateral hypothalamus (LH) has been ascribed to a population of orexin (ORX)-containing neurons that send projections to central areas which regulate Wake-Sleep and autonomic function...
  70. Kim S, Pilowsky P, Farnham M. Intrathecal Intermittent Orexin-A Causes Sympathetic Long-Term Facilitation and Sensitizes the Peripheral Chemoreceptor Response to Hypoxia in Rats. J Pharmacol Exp Ther. 2016;358:492-501 pubmed publisher
    ..of SNA, termed sympathetic long-term facilitation, after acute intermittent hypoxia (AIH) is caused by endogenous orexin acting on spinal sympathetic preganglionic neurons...
  71. Messina A, De Fusco C, Monda V, Esposito M, Moscatelli F, Valenzano A, et al. Role of the Orexin System on the Hypothalamus-Pituitary-Thyroid Axis. Front Neural Circuits. 2016;10:66 pubmed publisher
    Hypocretin/orexin (ORX) are two hypothalamic neuropeptides discovered in 1998. Since their discovery, they have been one of the most studied neuropeptide systems because of their projecting fields innervating various brain areas...
  72. Peyron C, Kilduff T. Mapping the Hypocretin/Orexin Neuronal System: An Unexpectedly Productive Journey. J Neurosci. 2017;37:2268-2272 pubmed publisher
    ..Neuroscience: a highly detailed anatomical description of the extensive axonal projections of the hypocretin/orexin neurons...
  73. Ogawa Y, Kanda T, Vogt K, Yanagisawa M. Anatomical and electrophysiological development of the hypothalamic orexin neurons from embryos to neonates. J Comp Neurol. 2017;525:3809-3820 pubmed publisher
    ..in the neonatal period, which is also observed in mature animals and human individuals lacking neuropeptide orexin/hypocretin signaling...
  74. Noseda R, Lee A, Nir R, Bernstein C, Kainz V, Bertisch S, et al. Neural mechanism for hypothalamic-mediated autonomic responses to light during migraine. Proc Natl Acad Sci U S A. 2017;114:E5683-E5692 pubmed publisher
    ..brainstem and spinal cord that regulate parasympathetic and sympathetic functions and contain dopamine, histamine, orexin, melanin-concentrating hormone, oxytocin, and vasopressin...
  75. 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
    ..The G protein-coupled receptors (GPCRs) for these ligands, the OX? and OX? orexin receptors, are more widely expressed throughout the central nervous system...
  76. Lee J, Bang E, Chae K, Kim J, Lee D, Lee W. Solution structure of a new hypothalamic neuropeptide, human hypocretin-2/orexin-B. Eur J Biochem. 1999;266:831-9 pubmed
    b>Orexin-A and orexin-B (also called hypocretin-1 and hypocretin-2, respectively) are novel hypothalamic neuropeptides encoded by a single mRNA transcript; they stimulate food intake...
  77. 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
    b>Orexin/hypocretin neurons are located in and around the perifornical hypothalamus...
  78. Herring W, Connor K, Snyder E, Snavely D, Zhang Y, Hutzelmann J, et al. Clinical profile of suvorexant for the treatment of insomnia over 3 months in women and men: subgroup analysis of pooled phase-3 data. Psychopharmacology (Berl). 2017;234:1703-1711 pubmed publisher
    ..To evaluate the clinical profile of suvorexant, a novel orexin receptor antagonist approved for treating insomnia at doses up to 20 mg, by sex subgroups...
  79. Aziz A, Fronczek R, Maat Schieman M, Unmehopa U, Roelandse F, Overeem S, et al. Hypocretin and melanin-concentrating hormone in patients with Huntington disease. Brain Pathol. 2008;18:474-83 pubmed publisher
    To evaluate whether hypocretin-1 (orexin-A) and melanin-concentrating hormone (MCH) neurotransmission are affected in patients with Huntington disease (HD), we immunohistochemically stained hypocretin and MCH neurons and estimated their ..
  80. Dohi K, Ripley B, Fujiki N, Ohtaki H, Yamamoto T, Goto Y, et al. CSF orexin-A/hypocretin-1 concentrations in patients with intracerebral hemorrhage (ICH). Regul Pept. 2008;145:60-4 pubmed
    ..Recent studies have suggested that the orexin system may also be involved in neuronal damage in the clinical setting and animal experiments...
  81. Bayerlein K, Kraus T, Leinonen I, Pilniok D, Rotter A, Hofner B, et al. Orexin A expression and promoter methylation in patients with alcohol dependence comparing acute and protracted withdrawal. Alcohol. 2011;45:541-7 pubmed publisher
    ..Therefore, the orexin A expression and promoter methylation in peripheral blood cells of 68 patients (41 male and 27 female patients at ..
  82. Karhu L, Turku A, Xhaard H. Modeling of the OX1R-orexin-A complex suggests two alternative binding modes. BMC Struct Biol. 2015;15:9 pubmed publisher
    Interactions between the orexin peptides and their cognate OX1 and OX2 receptors remain poorly characterized...
  83. Mäkelä K, Wigren H, Zant J, Sakurai T, Alhonen L, Kostin A, et al. Characterization of sleep-wake patterns in a novel transgenic mouse line overexpressing human prepro-orexin/hypocretin. Acta Physiol (Oxf). 2010;198:237-49 pubmed publisher
    b>Orexin/hypocretin peptides are expressed in the lateral hypothalamus and involved in the regulation of autonomic functions, energy homeostasis and arousal states...
  84. Zitnik G. Control of arousal through neuropeptide afferents of the locus coeruleus. Brain Res. 2016;1641:338-50 pubmed publisher
    ..These neuropeptides include: corticotropin releasing factor (CRF), orexin (ORX), endogenous opioids, substance P (SP), melanin-concentrating hormone (MCH), neuropeptide Y (NPY) and ..
  85. Dehkordi O, Rose J, Dávila García M, Millis R, Mirzaei S, Manaye K, et al. Neuroanatomical Relationships between Orexin/Hypocretin-Containing Neurons/Nerve Fibers and Nicotine-Induced c-Fos-Activated Cells of the Reward-Addiction Neurocircuitry. J Alcohol Drug Depend. 2017;5: pubmed publisher
    b>Orexin/hypocretin-containing neurons in lateral hypothalamus (LH) are implicated in the neurobiology of nicotine addiction...
  86. Hungs M, Lin L, Okun M, Mignot E. Polymorphisms in the vicinity of the hypocretin/orexin are not associated with human narcolepsy. Neurology. 2001;57:1893-5 pubmed
    Human narcolepsy/cataplexy is associated with reduced hypocretin (orexin) transmission...
  87. Ohta K, Kajiya M, Zhu T, Nishi H, Mawardi H, Shin J, et al. Additive effects of orexin B and vasoactive intestinal polypeptide on LL-37-mediated antimicrobial activities. J Neuroimmunol. 2011;233:37-45 pubmed publisher
    The present study examined the bactericidal effects of orexin B (ORXB) and vasoactive intestinal peptide (VIP) alone or combined with cationic antimicrobial peptides, such as LL-37, on Escherichia coli, Pseudomonas aeruginosa, ..
  88. Ahmed W, Tsutsumi M, Nakata S, Mori T, Nishimura Y, Fujisawa T, et al. A functional variation in the hypocretin neuropeptide precursor gene may be associated with obstructive sleep apnea syndrome in Japan. Laryngoscope. 2012;122:925-9 pubmed publisher
    ..4-fold and 1.5-fold increases in sera levels of orexin-A, respectively...
  89. Schmidt C, Leibiger J, Fendt M. The norepinephrine reuptake inhibitor reboxetine is more potent in treating murine narcoleptic episodes than the serotonin reuptake inhibitor escitalopram. Behav Brain Res. 2016;308:205-10 pubmed publisher
    ..b>Orexin-deficient mice were treated with different doses of the norepinephrine reuptake inhibitor reboxetine, the ..
  90. Smolinska N, Kiezun M, Dobrzyn K, Szeszko K, Maleszka A, Kaminski T. Adiponectin, orexin A and orexin B concentrations in the serum and uterine luminal fluid during early pregnancy of pigs. Anim Reprod Sci. 2017;178:1-8 pubmed publisher
    ..The neuropeptides orexin A (OXA, hypocretin-1) and orexin B (OXB, hypocretin-2) are derived from a common precursor peptide, prepro-orexin ..
  91. Ahmadi Soleimani S, Azizi H, Gompf H, Semnanian S. Role of orexin type-1 receptors in paragiganto-coerulear modulation of opioid withdrawal and tolerance: A site specific focus. Neuropharmacology. 2017;126:25-37 pubmed publisher
    b>Orexin-A and -B neuropeptides are exclusively synthesized in hypothalamic neurons...
  92. Kalamatianos T, Markianos M, Margetis K, Bourlogiannis F, Stranjalis G. Higher Orexin A levels in lumbar compared to ventricular CSF: a study in idiopathic normal pressure hydrocephalus. Peptides. 2014;51:1-3 pubmed publisher
    b>Orexin A (ORX-A) is implicated in the regulation of various physiological processes, including sleep/wake cycles and reward/motivation. The hypothalamic ORX-A neurons project throughout the brain and spinal cord...