Oreksinski receptor 2

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Hipokretinski (oreksinski) receptor 2
Identifikatori
SimboliHCRTR2; OX2R
Vanjski IDOMIM: 602393 MGI: 2680765 HomoloGene: 1168 IUPHAR: OX2 GeneCards: HCRTR2 Gene
Ontologija gena
Molekularna funkcija aktivnost rodopsinu-sličnog receptora
receptorska aktivnost
aktivnost neuropeptidnog receptora
aktivnost oreksinskog receptora
Celularna komponenta integralno sa ćelijskom membranom
membrana
Biološki proces prenos signala
G-proteinska signalizacija, spregnuto sa IP3 sekundarnim glasnikom (aktivacija fosfolipaze C)
neuropeptidni signalni put
sinapsna transmisija
ishrana
Pregled RNK izražavanja
podaci
Ortolozi
VrstaČovekMiš
Entrez3062387285
EnsemblENSG00000137252ENSMUSG00000032360
UniProtO43614Q8BV78
RefSeq (mRNA)NM_001526NM_198962
RefSeq (protein)NP_001517NP_945200
Lokacija (UCSC)Chr 6:
55.15 - 55.26 Mb
Chr 9:
76.01 - 76.11 Mb
PubMed pretraga[1][2]

Oreksinski receptor tip 2 (OX2R, OX2, ili hipokretinski receptor tip 2), je protein koji je kod ljudi kodiran HCRTR2 genom.[1]

Funkcija

OX2 je G-protein spregnuti receptor koji je isključivo izražen u mozgu. On je 64% identičan s OX1. OX2 vezuje oreksin A i oreksin B neuropeptide. OX2 učestvuje u centralnom povratnom mehanizmu koji reguliše unos hrane.[1]

Ligandi

Agonisti

  • Oreksin-A
  • Oreksin-B
  • SB-668,875

Antagonisti

  • Almoreksant - nespecifični OX1/2 antagonist
  • SB-649,868 - nespecifični OX1/2 antagonist
  • TCS-OX2-29 - selektivni OX2 antagonist
  • 1-(2,4-dibromofenil)-3-((4S,5S)-2,2-dimetil-4-fenil-[1,3]dioksan-5-il)urea (600 puta selektivniji za OX2 od OX1)[2]
  • (3,4-dimetoksifenoksi)alkilamino acetamidi[3]

Vidi još

Reference

  1. 1,0 1,1 „Entrez Gene: HCRTR2 hypocretin (orexin) receptor 2”. 
  2. McAtee, LC; Sutton, SW; Rudolph, DA; Li, X; Aluisio, LE; Phuong, VK; Dvorak, CA; Lovenberg, TW i dr.. (2004). „Novel substituted 4-phenyl-1,3dioxanes: potent and selective orexin receptor 2 (OX(2)R) antagonists”. Bioorganic & medicinal chemistry letters 14 (16): 4225–9. DOI:10.1016/j.bmcl.2004.06.032. PMID 15261275. 
  3. Cole, AG; Stroke, IL; Qin, LY; Hussain, Z; Simhadri, S; Brescia, MR; Waksmunski, FS; Strohl, B i dr.. (2008). „Synthesis of (3,4-dimethoxyphenoxy)alkylamino acetamides as orexin-2 receptor antagonists”. Bioorganic & medicinal chemistry letters 18 (20): 5420–3. DOI:10.1016/j.bmcl.2008.09.038. PMID 18815029. 

Literatura

  • Flier JS, Maratos-Flier E (1998). „Obesity and the hypothalamus: novel peptides for new pathways.”. Cell 92 (4): 437–40. DOI:10.1016/S0092-8674(00)80937-X. PMID 9491885. 
  • Willie JT, Chemelli RM, Sinton CM, Yanagisawa M (2001). „To eat or to sleep? Orexin in the regulation of feeding and wakefulness.”. Annu. Rev. Neurosci. 24: 429–58. DOI:10.1146/annurev.neuro.24.1.429. PMID 11283317. 
  • Hungs M, Mignot E (2001). „Hypocretin/orexin, sleep and narcolepsy.”. Bioessays 23 (5): 397–408. DOI:10.1002/bies.1058. PMID 11340621. 
  • de Lecea L, Kilduff TS, Peyron C, et al. (1998). „The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity.”. Proc. Natl. Acad. Sci. U.S.A. 95 (1): 322–7. DOI:10.1073/pnas.95.1.322. PMC 18213. PMID 9419374. 
  • Sakurai T, Amemiya A, Ishii M, et al. (1998). „Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior.” (PDF). Cell 92 (4): 573–85. DOI:10.1016/S0092-8674(00)80949-6. PMID 9491897. Arhivirano iz originala na datum 2011-07-11. Pristupljeno 2014-05-08. 
  • Sakurai T, Amemiya A, Ishii M, et al. (1998). „Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior.”. Cell 92 (5): 697. DOI:10.1016/S0092-8674(02)09256-5. PMID 9527442. 
  • Peyron C, Faraco J, Rogers W, et al. (2000). „A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains.”. Nat. Med. 6 (9): 991–7. DOI:10.1038/79690. PMID 10973318. 
  • Wright GJ, Puklavec MJ, Willis AC, et al. (2000). „Lymphoid/neuronal cell surface OX2 glycoprotein recognizes a novel receptor on macrophages implicated in the control of their function.”. Immunity 13 (2): 233–42. DOI:10.1016/S1074-7613(00)00023-6. PMID 10981966. 
  • Hartley JL, Temple GF, Brasch MA (2001). „DNA cloning using in vitro site-specific recombination.”. Genome Res. 10 (11): 1788–95. DOI:10.1101/gr.143000. PMC 310948. PMID 11076863. 
  • Mazzocchi G, Malendowicz LK, Gottardo L, et al. (2001). „Orexin A stimulates cortisol secretion from human adrenocortical cells through activation of the adenylate cyclase-dependent signaling cascade.”. J. Clin. Endocrinol. Metab. 86 (2): 778–82. DOI:10.1210/jc.86.2.778. PMID 11158046. 
  • Blanco M, López M, García-Caballero T, et al. (2001). „Cellular localization of orexin receptors in human pituitary.”. J. Clin. Endocrinol. Metab. 86 (4): 1616–9. DOI:10.1210/jc.86.4.1616. PMID 11297593. 
  • Blanco M, López M, GarcIa-Caballero T, et al. (2001). „Cellular localization of orexin receptors in human pituitary.”. J. Clin. Endocrinol. Metab. 86 (7): 3444–7. DOI:10.1210/jc.86.7.3444. PMID 11443222. 
  • Karteris E, Randeva HS, Grammatopoulos DK, et al. (2001). „Expression and coupling characteristics of the CRH and orexin type 2 receptors in human fetal adrenals.”. J. Clin. Endocrinol. Metab. 86 (9): 4512–9. DOI:10.1210/jc.86.9.4512. PMID 11549701. 
  • Randeva HS, Karteris E, Grammatopoulos D, Hillhouse EW (2001). „Expression of orexin-A and functional orexin type 2 receptors in the human adult adrenals: implications for adrenal function and energy homeostasis.”. J. Clin. Endocrinol. Metab. 86 (10): 4808–13. DOI:10.1210/jc.86.10.4808. PMID 11600545. 
  • Olafsdóttir BR, Rye DB, Scammell TE, et al. (2002). „Polymorphisms in hypocretin/orexin pathway genes and narcolepsy.”. Neurology 57 (10): 1896–9. PMID 11723285. 
  • Blanco M, García-Caballero T, Fraga M, et al. (2002). „Cellular localization of orexin receptors in human adrenal gland, adrenocortical adenomas and pheochromocytomas.”. Regul. Pept. 104 (1-3): 161–5. DOI:10.1016/S0167-0115(01)00359-7. PMID 11830291. 
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). „Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.”. Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. DOI:10.1073/pnas.242603899. PMC 139241. PMID 12477932. 

Spoljašnje veze

  • „Orexin Receptors: OX2”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Arhivirano iz originala na datum 2012-10-23. 
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Klasa A: Rodopsinu slični
α1 (A, B, D) • α2 (A, B, C) • β1 • β2 • β3
Adenozinski (A1, A2A, A2B, A3) • P2Y (1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14)
(svi osim 5-HT3) 5-HT1 (A, B, D, E, F) • 5-HT2 (A, B, C) • 5-HT (4, 5A, 6, 7)
Drugi
Acetilholin (M1, M2, M3, M4, M5) • Dopamin (D1, D2, D3, D4, D5) • Histamin (H1, H2, H3, H4) • Melatonin (1A, 1B, 1C) • TAAR (1, 2, 3, 5, 6, 8, 9)
Metaboliti i
signalni molekuli
CysLT (1, 2) • LTB4 (1, 2) • FPRL1 • OXE • Prostaglandin (DP (1, 2), EP (1, 2, 3, 4), FP) • Prostaciklin • Tromboksan
Drugi
Žučna kiselina • Kanabinoidni (CB1, CB2, GPR (18, 55, 119)) • EBI2 • Estrogen • Slobodna masna kiselina (1, 2, 3, 4) • Laktat  • Lizofosfatidna kiselina (1, 2, 3, 4, 5, 6)  • Lizofosfolipid (1, 2, 3, 4, 5, 6, 7, 8) • Niacin (1, 2) • Oksoglutarat • PAF • Sfingozin-1-fosfat (1, 2, 3, 4, 5) • Sukcinat
Peptid
B/W (1, 2) • FF (1, 2) • S • Y (1, 2, 4, 5) • Neuromedin (B, U (1, 2)) • Neurotenzin (1, 2)
Drugi
Anafilatoksin (C3a, C5a) • Angiotenzin (1, 2) • Apelin • Bombezin (BRS3, GRPR, NMBR) • Bradikinin (B1, B2) • Hemokin • Holecistokinin (A, B) • Endotelin (A, B) • Formil peptid (1, 2, 3) • FSH • Galanin (1, 2, 3) • GHB receptor • Gonadotropin-oslobađajući hormon (1, 2) • Grelin • Kispeptin • Luteinizirajući hormon/horiogonadotropin • MAS (1, 1L, D, E, F, G, X1, X2, X3, X4) • Melanokortin (1, 2, 3, 4, 5) • MCHR (1, 2) • Motilin • Opioidni (δ, κ, μ, Nociceptin & ζ, ali ne σ) • Oreksin (1, 2) • Oksitocin • Prokineticin (1, 2) • Prolaktin-oslobađajući peptid • Relaksin (1, 2, 3, 4) • Somatostatin (1, 2, 3, 4, 5) • Tahikinin (1, 2, 3) • Tirotropin • Tirotropin-oslobađajući hormon • Urotenzin-II • Vazopresin (1A, 1B, 2)
Razno
GPR (1, 3, 4, 6, 12, 15, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 31, 32, 33, 34, 35, 37, 39, 42, 44, 45, 50, 52, 55, 61, 62, 63, 65, 68, 75, 77, 78, 81, 82, 83, 84, 85, 87, 88, 92, 101, 103, 109A, 109B, 119, 120, 132, 135, 137B, 139, 141, 142, 146, 148, 149, 150, 151, 152, 153, 160, 161, 162, 171, 173, 174, 176, 177, 182, 183)
Drugi
Adrenomedulin • Mirisni • Opsin (3, 4, 5, 1LW, 1MW, 1SW, RGR, RRH) • Proteazom-aktivirani (1, 2, 3, 4) • SREB (1, 2, 3)
Klasa B: Sekretinu slični
GPR (56, 64, 97, 98, 110, 111, 112, 113, 114, 115, 116, 123, 124, 125, 126, 128, 133, 143, 144, 155, 157)
Drugi
Klasa C: Metabotropni
glutamat / feromon
TAS1R (1, 2, 3) • TAS2R (1, 3, 4, 5, 8, 9, 10, 12, 13, 14, 16, 19, 20, 30, 31, 38, 39, 40, 41, 42, 43, 45, 46, 50)
Drugi
Klasa F:
Frizzled / Zaglađeni
Uvojiti
Frizzled (1, 2, 3, 4, 5, 6, 7, 8, 9, 10)
Zaglađeni
B trdu: peptidi (nrpl/grfl/cytl/horl), receptori (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd, signalni putevi (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
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Neuropeptidni receptori
Hormonski receptori
Drugi
Opioidni receptori
Drugi neuropeptidni receptori
B trdu: peptidi (nrpl/grfl/cytl/horl), receptori (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd, signalni putevi (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
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Holecistokinin
CCKA
Agonisti: Holecistokinin • CCK-4
Antagonisti: Asperlicin • Proglumid • Lorglumid • Devazepid • Deksloksiglumid
CCKB
Agonisti: Holecistokinin • CCK-4 • Gastrin
Antagonisti: Proglumid • CI-988
CRH
CRF1
CRF2
Galanin
GAL1
Agonisti: Galanin • Galaninu-sličan peptid • Galmic • Galnon
GAL2
Agonisti: Galanin • Galaninu-sličan peptid • Galmic • Galnon
GAL3
Agonisti: Galanin • Galmic • Galnon
Grelin
Agonisti: Grelin • Kapromorelin • MK-677 • Sermorelin • SM-130,686 • Tabimorelin
MCH
MCH1
MCH2
Melanokortin
MC1
MC2
Agonisti: ACTH • Kosintropin • Tetrakosaktid
MC3
Agonisti: alfa-MSH • Bremelanotid • Melanotan II
MC4
Agonisti: alfa-MSH • Bremelanotid • Melanotan II • THIQ
Antagonisti: Agutiju srodni peptid
MC5
Agonisti: alfa-MSH • Melanotan II
Neuropeptid S
Agonisti: Neuropeptid S
Antagonisti: SHA-68
Neuropeptid Y
Y1
Agonisti: Neuropeptid Y • Peptid YY
Antagonisti: BIBP-3226
Y2
Agonisti: Neuropeptid Y • Peptid YY
Antagonisti: BIIE-0246
Y4
Agonisti: Neuropeptid Y • Pankreasni polipeptid • Peptid YY
Antagonisti: UR-AK49
Y5
Agonisti: Neuropeptid Y • Peptid YY
Antagonisti: Lu AA-33810
Neurotenzin
NTS1
Agonisti: Neurotenzin • Neuromedin N
Antagonisti: SR-48692 • SR-142,948
NTS2
Agonisti: Neurotenzin
Antagonisti: Levokabastin • SR-142,948
Opioid
vidi Opioidi
Oreksin
OX1
Agonisti: Oreksin-A
Antagonisti: Almoreksant • SB-334,867 • SB-408,124 • SB-649,868
OX2
Agonisti: Oreksin-A
Antagonisti: Almoreksant • SB-649,868 • TCS-OX2-29
Oksitocin
Agonisti: Karbetocin • Demoksitocin • Oksitocin • WAY-267,464
Antagonisti: Atosiban • L-371,257 • L-368,899
Tahikinin
NK1
Agonisti: Supstanca P
Antagonisti: Aprepitant • Befetupitant • Kasopitant • CI-1021 • CP-96,345 • CP-99,994 • CP-122,721 • Dapitant • Ezlopitant • FK-888 • Fosaprepitant • GR-203,040 • GW-597,599 • HSP-117 • L-733,060 • L-741,671 • L-743,310 • L-758,298 • Lanepitant • LY-306,740 • Maropitant • Netupitant • NKP-608 • Nolpitantium • Orvepitant • RP-67,580 • SDZ NKT 343 • Vestipitant • Vofopitant
NK2
Agonisti: Neurokinin A
Antagonisti: GR-159897 • Ibodutant • Saredutant
NK3
Agonisti: Neurokinin B
Antagonisti: Osanetant • Talnetant
Vazopresin
V1A
Agonisti: Dezmopresin • Felipresin • Ornipresin • Terlipresin • Vazopresin
Antagonisti: Konivaptan • Demeklociklin • Relkovaptan
V1B
Agonisti: Felipresin • Ornipresin • Terlipresin • Vazopresin
Antagonisti: Demeklociklin • Nelivaptan
V2
Agonisti: Dezmopresin • Ornipresin • Vazopresin
Antagonisti: Konivaptan • Demeklociklin • Liksivaptan • Mozavaptan • Satavaptan • Tolvaptan