PR01522

OREXIN2R

PRINTS entry
Member databasePRINTS
PRINTS typefamily
Short nameOREXIN2R

Description
Imported from IPR004060

The neuropeptide hormone orexin stimulates appetite and food consumption
[9]
, and is found in the hypothalamus, which has been shown to be the 'feeding centre' and plays a central role in the integrated control of feeding and energy homeostasis
[8]
. It also has a prominent role in promoting wakefulness
[7, 5, 13]
. The orexin receptor (also referred to as the hypocretin receptor) is a rhodopsin-like G protein-coupled receptor that binds orexin. There are two subtypes; orexin receptor 1 (OX1) and orexin receptor 2 (OX2)
[3]
.

This entry represents Orexin receptor 2, which is found throughout vertebrates and, like OX1, is expressed in brainstem and striatal nuclei, with additional expression in arousal promoting histaminergic nuclei
[4, 1, 12]
. Both Orexin-A and B have nearly equal affinity for OX2
[8]
, and stimulate intracellular calcium levels through OX2-mediated induction of Gq and phospholipase C activity, but is also capable of activating Gs, Gi, and potentially ion channels
[6, 2, 11, 11]
. The OX2 receptor predominantly mediate the control of arousal induced by orexin neuropeptides
[10, 7]
.

References
Imported from IPR004060

1.Orexins and their receptors from fish to mammals: a comparative approach. Wong KK, Ng SY, Lee LT, Ng HK, Chow BK. Gen. Comp. Endocrinol. 171, 124-30, (2011). View articlePMID: 21216246

2.Orexin signaling in recombinant neuron-like cells. Holmqvist T, Akerman KE, Kukkonen JP. FEBS Lett. 526, 11-4, (2002). View articlePMID: 12208495

3.Orexins in the regulation of the hypothalamic-pituitary-adrenal axis. Spinazzi R, Andreis PG, Rossi GP, Nussdorfer GG. Pharmacol. Rev. 58, 46-57, (2006). View articlePMID: 16507882

4.Distribution of orexin receptor mRNA in the rat brain. Trivedi P, Yu H, MacNeil DJ, Van der Ploeg LH, Guan XM. FEBS Lett. 438, 71-5, (1998). View articlePMID: 9821961

5.Hypocretin (orexin) deficiency in human narcolepsy. Nishino S, Ripley B, Overeem S, Lammers GJ, Mignot E. Lancet 355, 39-40, (2000). View articlePMID: 10615891

6.Characterization of recombinant human orexin receptor pharmacology in a Chinese hamster ovary cell-line using FLIPR. Smart D, Jerman JC, Brough SJ, Rushton SL, Murdock PR, Jewitt F, Elshourbagy NA, Ellis CE, Middlemiss DN, Brown F. Br. J. Pharmacol. 128, 1-3, (1999). View articlePMID: 10498827

7.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 PJ, Nishino S, Mignot E. Cell 98, 365-76, (1999). View articlePMID: 10458611

8.Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. 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. Cell 92, 573-85, (1998). View articlePMID: 9491897

9.Orexins: a newly discovered family of hypothalamic regulators of food intake. Wolf G. Nutr. Rev. 56, 172-3, (1998). PMID: 9656726

10.Distinct narcolepsy syndromes in Orexin receptor-2 and Orexin null mice: molecular genetic dissection of Non-REM and REM sleep regulatory processes. Willie JT, Chemelli RM, Sinton CM, Tokita S, Williams SC, Kisanuki YY, Marcus JN, Lee C, Elmquist JK, Kohlmeier KA, Leonard CS, Richardson JA, Hammer RE, Yanagisawa M. Neuron 38, 715-30, (2003). View articlePMID: 12797957

11.Expression of orexin-A and functional orexin type 2 receptors in the human adult adrenals: implications for adrenal function and energy homeostasis. Randeva HS, Karteris E, Grammatopoulos D, Hillhouse EW. J. Clin. Endocrinol. Metab. 86, 4808-13, (2001). View articlePMID: 11600545

12.Differential expression of orexin receptors 1 and 2 in the rat brain. Marcus JN, Aschkenasi CJ, Lee CE, Chemelli RM, Saper CB, Yanagisawa M, Elmquist JK. J. Comp. Neurol. 435, 6-25, (2001). View articlePMID: 11370008

13.Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Chemelli RM, Willie JT, Sinton CM, Elmquist JK, Scammell T, Lee C, Richardson JA, Williams SC, Xiong Y, Kisanuki Y, Fitch TE, Nakazato M, Hammer RE, Saper CB, Yanagisawa M. Cell 98, 437-51, (1999). View articlePMID: 10481909

Supplementary References

1. Fingerprinting G-protein-coupled receptors. Attwood TK, Findlay JB. Protein Eng. 7, 195-203, (1994). View articlePMID: 8170923

2. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. 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. Cell 92, 1 page following 696, (1998). View articlePMID: 9527442

3. G proteins in signal transduction. Birnbaumer L. Annu. Rev. Pharmacol. Toxicol. 30, 675-705, (1990). View articlePMID: 2111655

4. Orexin receptor type-1 couples exclusively to pertussis toxin-insensitive G-proteins, while orexin receptor type-2 couples to both pertussis toxin-sensitive and -insensitive G-proteins. Zhu Y, Miwa Y, Yamanaka A, Yada T, Shibahara M, Abe Y, Sakurai T, Goto K. J. Pharmacol. Sci. 92, 259-66, (2003). View articlePMID: 12890892

5. G protein involvement in receptor-effector coupling. Casey PJ, Gilman AG. J. Biol. Chem. 263, 2577-80, (1988). View articlePMID: 2830256

6. Orexin receptors and G-protein coupling: evidence for another "promiscuous" seven transmembrane domain receptor. Karteris E, Randeva HS. J. Pharmacol. Sci. 93, 126-8, (2003). View articlePMID: 14501163

7. Obesity and the hypothalamus: novel peptides for new pathways. Flier JS, Maratos-Flier E. Cell 92, 437-40, (1998). View articlePMID: 9491885

8. Design of a discriminating fingerprint for G-protein-coupled receptors. Attwood TK, Findlay JB. Protein Eng. 6, 167-76, (1993). View articlePMID: 8386361

Integrated to
This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our Privacy Notice and Terms of Use.