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Gene Review

HCRT  -  hypocretin (orexin) neuropeptide precursor

Homo sapiens

Synonyms: Hcrt, Hypocretin, NRCLP1, OX, Orexin, ...
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Disease relevance of HCRT


Psychiatry related information on HCRT


High impact information on HCRT


Chemical compound and disease context of HCRT


Biological context of HCRT

  • METHODS: We performed association studies on the insertion/deletion (I/D) sequence polymorphism of ACE and single nucleotide polymorphisms within the prepro-orexin (HCRT), orexin receptor 1 (HCRTR1), and orexin receptor 2 (HCRTR2) genes [7].
  • Although hypocretin loci do not contribute significantly to genetic predisposition, most cases of human narcolepsy are associated with a deficient hypocretin system [6].
  • We deconvolved 24-h plasma profiles of ACTH and cortisol, and determined their circadian rhythm by cosinor analysis in seven hypocretin-deficient narcoleptic males and seven matched controls [19].
  • RESULTS: There was no significant difference in the total number of hypocretin-containing neurons among the seven PWS patients (in whom sufficient hypothalamic material was available to quantify total cell number) and seven age-matched controls, either in adults or in infants [1].
  • Interestingly, we found inter-individual differences in methylation levels in HTR2A and HCRT in the placenta and in some loci of HERV-K in the placenta and liver [20].

Anatomical context of HCRT


Associations of HCRT with chemical compounds


Regulatory relationships of HCRT


Other interactions of HCRT


Analytical, diagnostic and therapeutic context of HCRT

  • DESIGN: We estimated the number of hypocretin neurons in postmortem hypothalami using immunocytochemistry and an image analysis system [1].
  • Electrical stimulation of hypothalamic microslices that contained hypocretin cells and their axons evoked dynorphin release [36].
  • High-resolution CT (HCRT) is extremely helpful in understanding pathomorphological changes, mode of spread of the disease, and sequential morphological change after antituberculous chemotherapy, and possibly in diagnosing activity of the disease [37].
  • In contrast to these animal models, most human narcolepsy is not familial, is discordant in identical twins, and has not been linked to mutations of the Hcrt system [5].
  • We provide evidence for the role of endogenously produced hypocretin/orexin in the physiological response to immobilization stress and identify the receptor subtype responsible for this action of the peptide [38].


  1. The number of hypothalamic hypocretin (orexin) neurons is not affected in Prader-Willi syndrome. Fronczek, R., Lammers, G.J., Balesar, R., Unmehopa, U.A., Swaab, D.F. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  2. Relationship between CSF hypocretin levels and hypocretin neuronal loss. Gerashchenko, D., Murillo-Rodriguez, E., Lin, L., Xu, M., Hallett, L., Nishino, S., Mignot, E., Shiromani, P.J. Exp. Neurol. (2003) [Pubmed]
  3. Emphysema in heavy smokers with normal chest radiography. Detection and quantification by HCRT. Sashidhar, K., Gulati, M., Gupta, D., Monga, S., Suri, S. Acta radiologica (Stockholm, Sweden : 1987) (2002) [Pubmed]
  4. Treatment of T3 and T4 carcinomas of the gallbladder. Okamoto, A., Tsuruta, K., Ishiwata, J., Isawa, T., Kamisawa, T., Tanaka, Y. International surgery. (1996) [Pubmed]
  5. Reduced number of hypocretin neurons in human narcolepsy. Thannickal, T.C., Moore, R.Y., Nienhuis, R., Ramanathan, L., Gulyani, S., Aldrich, M., Cornford, M., Siegel, J.M. Neuron (2000) [Pubmed]
  6. A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Peyron, C., Faraco, J., Rogers, W., Ripley, B., Overeem, S., Charnay, Y., Nevsimalova, S., Aldrich, M., Reynolds, D., Albin, R., Li, R., Hungs, M., Pedrazzoli, M., Padigaru, M., Kucherlapati, M., Fan, J., Maki, R., Lammers, G.J., Bouras, C., Kucherlapati, R., Nishino, S., Mignot, E. Nat. Med. (2000) [Pubmed]
  7. Association of an orexin 1 receptor 408Val variant with polydipsia-hyponatremia in schizophrenic subjects. Meerabux, J., Iwayama, Y., Sakurai, T., Ohba, H., Toyota, T., Yamada, K., Nagata, R., Irukayama-Tomobe, Y., Shimizu, H., Yoshitsugu, K., Ohta, K., Yoshikawa, T. Biol. Psychiatry (2005) [Pubmed]
  8. Genes for normal sleep and sleep disorders. Tafti, M., Maret, S., Dauvilliers, Y. Ann. Med. (2005) [Pubmed]
  9. Effects of IV and ICV hypocretin-1 (orexin A) in hypocretin receptor-2 gene mutated narcoleptic dogs and IV hypocretin-1 replacement therapy in a hypocretin-ligand-deficient narcoleptic dog. Fujiki, N., Yoshida, Y., Ripley, B., Mignot, E., Nishino, S. Sleep. (2003) [Pubmed]
  10. The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Lin, L., Faraco, J., Li, R., Kadotani, H., Rogers, W., Lin, X., Qiu, X., de Jong, P.J., Nishino, S., Mignot, E. Cell (1999) [Pubmed]
  11. The role of hypocretins (orexins) in sleep regulation and narcolepsy. Taheri, S., Zeitzer, J.M., Mignot, E. Annu. Rev. Neurosci. (2002) [Pubmed]
  12. The hypocretin/orexin ligand-receptor system: implications for sleep and sleep disorders. Kilduff, T.S., Peyron, C. Trends Neurosci. (2000) [Pubmed]
  13. Sleeping with the hypothalamus: emerging therapeutic targets for sleep disorders. Mignot, E., Taheri, S., Nishino, S. Nat. Neurosci. (2002) [Pubmed]
  14. Decreased brain histamine content in hypocretin/orexin receptor-2 mutated narcoleptic dogs. Nishino, S., Fujiki, N., Ripley, B., Sakurai, E., Kato, M., Watanabe, T., Mignot, E., Yanai, K. Neurosci. Lett. (2001) [Pubmed]
  15. Metabolic mechanism of wakefulness (and hunger) and sleep (and satiety): role of adenosine triphosphate and hypocretin and other peptides. Nicolaidis, S. Metab. Clin. Exp. (2006) [Pubmed]
  16. What keeps us awake: the neuropharmacology of stimulants and wakefulness-promoting medications. Boutrel, B., Koob, G.F. Sleep. (2004) [Pubmed]
  17. Sleep neurobiology for the clinician. España, R.A., Scammell, T.E. Sleep. (2004) [Pubmed]
  18. Report of a case of immunosuppression with prednisone in an 8-year-old boy with an acute onset of hypocretin-deficiency narcolepsy. Hecht, M., Lin, L., Kushida, C.A., Umetsu, D.T., Taheri, S., Einen, M., Mignot, E. Sleep. (2003) [Pubmed]
  19. Dynamics of the pituitary-adrenal ensemble in hypocretin-deficient narcoleptic humans: blunted basal adrenocorticotropin release and evidence for normal time-keeping by the master pacemaker. Kok, S.W., Roelfsema, F., Overeem, S., Lammers, G.J., Strijers, R.L., Frölich, M., Meinders, A.E., Pijl, H. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  20. Tissue specificity of methylation and expression of human genes coding for neuropeptides and their receptors, and of a human endogenous retrovirus K family. Shen, H.M., Nakamura, A., Sugimoto, J., Sakumoto, N., Oda, T., Jinno, Y., Okazaki, Y. J. Hum. Genet. (2006) [Pubmed]
  21. Hypocretin/orexin, sleep and narcolepsy. Hungs, M., Mignot, E. Bioessays (2001) [Pubmed]
  22. Hypocretin stimulates [(35)S]GTP gamma S binding in Hcrtr 2-transfected cell lines and in brain homogenate. Shiba, T., Ozu, M., Yoshida, Y., Mignot, E., Nishino, S. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  23. Diurnal variation of cerebrospinal fluid hypocretin-1 (Orexin-A) levels in control and depressed subjects. Salomon, R.M., Ripley, B., Kennedy, J.S., Johnson, B., Schmidt, D., Zeitzer, J.M., Nishino, S., Mignot, E. Biol. Psychiatry (2003) [Pubmed]
  24. Hypocretin/orexin selectively increases dopamine efflux within the prefrontal cortex: involvement of the ventral tegmental area. Vittoz, N.M., Berridge, C.W. Neuropsychopharmacology (2006) [Pubmed]
  25. Hypocretin-2-saporin lesions of the lateral hypothalamus produce narcoleptic-like sleep behavior in the rat. Gerashchenko, D., Kohls, M.D., Greco, M., Waleh, N.S., Salin-Pascual, R., Kilduff, T.S., Lappi, D.A., Shiromani, P.J. J. Neurosci. (2001) [Pubmed]
  26. The neurotransmitters of sleep. Siegel, J.M. The Journal of clinical psychiatry. (2004) [Pubmed]
  27. Role of executive function in ADHD. Swanson, J.M. The Journal of clinical psychiatry. (2003) [Pubmed]
  28. A systematic review of modafinil: potential clinical uses and mechanisms of action. Ballon, J.S., Feifel, D. The Journal of clinical psychiatry. (2006) [Pubmed]
  29. Hypocretin (orexin) receptor subtypes differentially enhance acetylcholine release and activate g protein subtypes in rat pontine reticular formation. Bernard, R., Lydic, R., Baghdoyan, H.A. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  30. The neurohormone orexin stimulates hypoxia-inducible factor-1 activity. Sikder, D., Kodadek, T. Genes Dev. (2007) [Pubmed]
  31. Detection of autoantibodies against hypocretin, hcrtrl, and hcrtr2 in narcolepsy: anti-Hcrt system antibody in narcolepsy. Tanaka, S., Honda, Y., Inoue, Y., Honda, M. Sleep. (2006) [Pubmed]
  32. Presynaptic and postsynaptic actions and modulation of neuroendocrine neurons by a new hypothalamic peptide, hypocretin/orexin. van den Pol, A.N., Gao, X.B., Obrietan, K., Kilduff, T.S., Belousov, A.B. J. Neurosci. (1998) [Pubmed]
  33. Narcolepsy and the hypocretins. Wurtman, R.J. Metab. Clin. Exp. (2006) [Pubmed]
  34. CSF hypocretin-1 levels in schizophrenics and controls: relationship to sleep architecture. Nishino, S., Ripley, B., Mignot, E., Benson, K.L., Zarcone, V.P. Psychiatry research. (2002) [Pubmed]
  35. Hypersomnia and low CSF hypocretin-1 (orexin-A) concentration in a patient with multiple sclerosis showing bilateral hypothalamic lesions. Kato, T., Kanbayashi, T., Yamamoto, K., Nakano, T., Shimizu, T., Hashimoto, T., Ikeda, S. Intern. Med. (2003) [Pubmed]
  36. Differential target-dependent actions of coexpressed inhibitory dynorphin and excitatory hypocretin/orexin neuropeptides. Li, Y., van den Pol, A.N. J. Neurosci. (2006) [Pubmed]
  37. CT of pulmonary tuberculosis. Im, J.G., Itoh, H., Han, M.C. Semin. Ultrasound CT MR (1995) [Pubmed]
  38. Hypocretin/orexin type 1 receptor in brain: role in cardiovascular control and the neuroendocrine response to immobilization stress. Samson, W.K., Bagley, S.L., Ferguson, A.V., White, M.M. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2007) [Pubmed]
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