Hypocretin (orexin) receptor 1 explained

Orexin receptor type 1 (Ox1R or OX₁), also known as hypocretin receptor type 1 (HcrtR1), is a protein that in humans is encoded by the HCRTR1 gene.^[1]

Function

The orexin 1 receptor (OX₁), is a G-protein coupled receptor that is heavily expressed in projections from the lateral hypothalamus and is involved in the regulation of feeding behaviour. OX₁ selectively binds the orexin-A neuropeptide. It shares 64% identity with OX₂.

Ligands

Agonists

• Orexin-A

Antagonists

• RTIOX-276 - Selective OX₁ antagonist
• ACT-335827 - Selective OX₁ antagonist
• Almorexant - Dual OX₁ and OX₂ antagonist
• Lemborexant - Dual OX₁ and OX₂ antagonist^[2]
• Nemorexant - Dual OX₁ and OX₂ antagonist
• SB-334,867 - Selective OX₁ antagonist
• SB-408,124 - Selective OX₁ antagonist
• SB-649,868 - Dual OX₁ and OX₂ antagonist
• Suvorexant - Dual OX₁ and OX₂ antagonist

See also

• Orexin receptor

External links

• Web site: Orexin Receptors: OX₁ . IUPHAR Database of Receptors and Ion Channels . International Union of Basic and Clinical Pharmacology . 2008-12-09 . 2016-02-06 . https://web.archive.org/web/20160206032935/http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=3012 . dead .

Further reading

• Flier JS, Maratos-Flier E . Obesity and the hypothalamus: novel peptides for new pathways . Cell . 92 . 4 . 437–40 . Feb 1998 . 9491885 . 10.1016/S0092-8674(00)80937-X . 14768585 . free .
• Willie JT, Chemelli RM, Sinton CM, Yanagisawa M . To eat or to sleep? Orexin in the regulation of feeding and wakefulness . Annual Review of Neuroscience . 24 . 429–58 . 2001 . 11283317 . 10.1146/annurev.neuro.24.1.429 .
• Hungs M, Mignot E . Hypocretin/orexin, sleep and narcolepsy . BioEssays . 23 . 5 . 397–408 . May 2001 . 11340621 . 10.1002/bies.1058 . 541650 .
• de Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE, Fukuhara C, Battenberg EL, Gautvik VT, Bartlett FS, Frankel WN, van den Pol AN, Bloom FE, Gautvik KM, Sutcliffe JG . The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity . Proceedings of the National Academy of Sciences of the United States of America . 95 . 1 . 322–7 . Jan 1998 . 9419374 . 18213 . 10.1073/pnas.95.1.322 . 1998PNAS...95..322D . free .
• Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, Williams SC, Richardson JA, Kozlowski GP, Wilson S, Arch JR, Buckingham RE, Haynes AC, Carr SA, Annan RS, McNulty DE, Liu WS, Terrett JA, Elshourbagy NA, Bergsma DJ, Yanagisawa M . Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior . Cell . 92 . 4 . 573–85 . Feb 1998 . 9491897 . 10.1016/S0092-8674(00)80949-6 . 16294729 . free .
• Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, Williams SC, Richarson JA, Kozlowski GP, Wilson S, Arch JR, Buckingham RE, Haynes AC, Carr SA, Annan RS, McNulty DE, Liu WS, Terrett JA, Elshourbagy NA, Bergsma DJ, Yanagisawa M . Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior . Cell . 92 . 5 . 1 page following 696 . Mar 1998 . 9527442 . 10.1016/S0092-8674(02)09256-5 . free .
• 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 GJ, Bouras C, Kucherlapati R, Nishino S, Mignot E . A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains . Nature Medicine . 6 . 9 . 991–7 . Sep 2000 . 10973318 . 10.1038/79690 . 18076282 .
• Blanco M, López M, GarcIa-Caballero T, Gallego R, Morel G, SeñarIs R, Casanueva F, Diéguez C, Beiras A . Cellular localization of orexin receptors in human pituitary . The Journal of Clinical Endocrinology and Metabolism . 86 . 7 . 1616–9 . Jul 2001 . 10.1210/jcem.86.7.7433 . 11443222 . free .
• Olafsdóttir BR, Rye DB, Scammell TE, Matheson JK, Stefánsson K, Gulcher JR . Polymorphisms in hypocretin/orexin pathway genes and narcolepsy . Neurology . 57 . 10 . 1896–9 . Nov 2001 . 11723285 . 10.1212/wnl.57.10.1896 . 38597998 .
• Wieland HA, Söll RM, Doods HN, Stenkamp D, Hurnaus R, Lämmle B, Beck-Sickinger AG . The SK-N-MC cell line expresses an orexin binding site different from recombinant orexin 1-type receptor . European Journal of Biochemistry . 269 . 4 . 1128–35 . Feb 2002 . 11856342 . 10.1046/j.0014-2956.2001.02739.x . free .
• Hilairet S, Bouaboula M, Carrière D, Le Fur G, Casellas P . Hypersensitization of the Orexin 1 receptor by the CB1 receptor: evidence for cross-talk blocked by the specific CB1 antagonist, SR141716 . The Journal of Biological Chemistry . 278 . 26 . 23731–7 . Jun 2003 . 12690115 . 10.1074/jbc.M212369200 . free .
• Karteris E, Chen J, Randeva HS . Expression of human prepro-orexin and signaling characteristics of orexin receptors in the male reproductive system . The Journal of Clinical Endocrinology and Metabolism . 89 . 4 . 1957–62 . Apr 2004 . 15070969 . 10.1210/jc.2003-031778 . free .
• Holmqvist T, Johansson L, Ostman M, Ammoun S, Akerman KE, Kukkonen JP . OX1 orexin receptors couple to adenylyl cyclase regulation via multiple mechanisms . The Journal of Biological Chemistry . 280 . 8 . 6570–9 . Feb 2005 . 15611118 . 10.1074/jbc.M407397200 . free .
• Spinazzi R, Rucinski M, Neri G, Malendowicz LK, Nussdorfer GG . Preproorexin and orexin receptors are expressed in cortisol-secreting adrenocortical adenomas, and orexins stimulate in vitro cortisol secretion and growth of tumor cells . The Journal of Clinical Endocrinology and Metabolism . 90 . 6 . 3544–9 . Jun 2005 . 15797953 . 10.1210/jc.2004-2385 . free .
• 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 . Association of an orexin 1 receptor 408Val variant with polydipsia-hyponatremia in schizophrenic subjects . Biological Psychiatry . 58 . 5 . 401–7 . Sep 2005 . 15978554 . 10.1016/j.biopsych.2005.04.015 . 26813056 .
• Ziolkowska A, Spinazzi R, Albertin G, Nowak M, Malendowicz LK, Tortorella C, Nussdorfer GG . Orexins stimulate glucocorticoid secretion from cultured rat and human adrenocortical cells, exclusively acting via the OX1 receptor . The Journal of Steroid Biochemistry and Molecular Biology . 96 . 5 . 423–9 . Sep 2005 . 16157481 . 10.1016/j.jsbmb.2005.05.003 . 27293941 .

Notes and References

1. Web site: Entrez Gene: HCRTR1 hypocretin (orexin) receptor 1.
2. Web site: Eisai Demonstrates Efficacy of Investigational Dual Orexin Receptor Antagonist E2006 in Sleep Initiation and Maintenance Data from Phase II Clinical Trial for Insomnia.