Kortikotropin-oslobađajući hormonski receptor 1

Identifikatori

CRHR1; CRF-R; CRF1; CRFR1; CRH-R1h; CRHR1f

Vanjski ID

OMIM: 122561 MGI: 88498 HomoloGene: 20920 IUPHAR: CRF₁ GeneCards: CRHR1 Gene

Ontologija gena
Molekularna funkcija	• receptorska aktivnost • aktivnost G-protein spregnutog receptora • aktivnost receptora kortikotropin-oslobađajućeg faktora
Celularna komponenta	• ćelijska membrana • integralno sa ćelijskom membranom • membrana
Biološki proces	• respons na stres • imunski respons • prenos signala • signalni put G-protein spregnutog receptora • G-protein signalizacija, spregnuta sa cAMP nukleotidnim sekundarnim glasnikom • aktivacija adenilat ciklaze • trudnoća • porođaj • ponašanje

Pregled RNK izražavanja

podaci

Ortolozi

Vrsta

Čovek

Miš

Entrez

1394

12921

Ensembl

ENSG00000120088

ENSMUSG00000018634

UniProt

P34998

Q0VGH2

RefSeq (mRNA)

XM_001128344

NM_007762

RefSeq (protein)

XP_001128344

NP_031788

Lokacija (UCSC)

Chr 17:
41.24 - 41.27 Mb

Chr 11:
103.95 - 103.99 Mb

PubMed pretraga

[1]

[2]

Kortikotropin-oslobađajući hormonski receptor 1 (CRHR1, CRF₁) je protein koji je kod ljudi kodiran CRHR1 genom.^[1]^[2]^[3]

Funkcija

Kortikotropin-oslobađajući hormonski receptor vezuje kortikotropin-oslobađajući hormon, potentan posrednik endokrinog, autonomnog, i imunskog responsa na stres.^[4]

Kod miševa CRF1 receptori posreduju etanolno pojačanje GABAergične sinaptičke transmisije.^[5]

Klinički značaj

Varijacije CRHR1 gena su povezane za povećanjem odgovora na inhalacionu kortikosteroidnu terapiju kod astme.^[6] Antagonisti CRF1 receptora se aktivno ispituju kao mogući tretman za depresiju i anksioznost.^[7]^[8]

Interakcije

Za kortikotropin-oslobađajući hormonski receptor 1 je pokazano da interaguje sa kortikotropin-oslobađajućim hormonom^[9]^[10] i urokortinom.^[10]^[11]

Vidi još

Kortikotropin-oslobađajući hormon
Kortikotropin-oslobađajući hormonski receptor
Kortikotropin-oslobađajući hormonski antagonisti
Antalarmin

Reference

^ Hauger RL, Grigoriadis DE, Dallman MF, Plotsky PM, Vale WW, Dautzenberg FM (2003). „International Union of Pharmacology. XXXVI. Current status of the nomenclature for receptors for corticotropin-releasing factor and their ligands”. Pharmacol. Rev. 55 (1): 21—6. PMID 12615952. doi:10.1124/pr.55.1.3.
^ Polymeropoulos MH, Torres R, Yanovski JA, Chandrasekharappa SC, Ledbetter DH (1995). „The human corticotropin-releasing factor receptor (CRHR) gene maps to chromosome 17q12-q22”. Genomics. 28 (1): 123—4. PMID 7590738. doi:10.1006/geno.1995.1118.
^ Chen R, Lewis KA, Perrin MH, Vale WW (1993). „Expression cloning of a human corticotropin-releasing-factor receptor”. Proc. Natl. Acad. Sci. U.S.A. 90 (19): 8967—71. PMC 47482 . PMID 7692441. doi:10.1073/pnas.90.19.8967.
^ „Entrez Gene: CRHR1 corticotropin releasing hormone receptor 1”.
^ Nie Z, Schweitzer P, Roberts AJ, Madamba SG, Moore SD, Siggins GR (2004). „Ethanol augments GABAergic transmission in the central amygdala via CRF1 receptors”. Science (journal). 303 (5663): 1512—4. PMID 15001778. doi:10.1126/science.1092550.
^ Tantisira KG, Lake S, Silverman ES, Palmer LJ, Lazarus R, Silverman EK, Liggett SB, Gelfand EW, Rosenwasser LJ, Richter B, Israel E, Wechsler M, Gabriel S, Altshuler D, Lander E, Drazen J, Weiss ST (2004). „Corticosteroid pharmacogenetics: association of sequence variants in CRHR1 with improved lung function in asthmatics treated with inhaled corticosteroids”. Hum. Mol. Genet. 13 (13): 1353—9. PMID 15128701. doi:10.1093/hmg/ddh149.
^ Kehne JH (2007). „The CRF1 receptor, a novel target for the treatment of depression, anxiety, and stress-related disorders”. CNS Neurol Disord Drug Targets. 6 (3): 163—82. PMID 17511614. doi:10.2174/187152707780619344.
^ Ising M, Holsboer F (2007). „CRH-sub-1 receptor antagonists for the treatment of depression and anxiety”. Exp Clin Psychopharmacol. 15 (6): 519—28. PMID 18179304. doi:10.1037/1064-1297.15.6.519.
^ Grammatopoulos, D K; Dai Y; et al. (1999). „A novel spliced variant of the type 1 corticotropin-releasing hormone receptor with a deletion in the seventh transmembrane domain present in the human pregnant term myometrium and fetal membranes”. Mol. Endocrinol. UNITED STATES. 13 (12): 2189—202. ISSN 0888-8809. PMID 10598591. doi:10.1210/me.13.12.2189.
^ ^а ^б Gottowik, J; Goetschy V; et al. (1997). „Labelling of CRF1 and CRF2 receptors using the novel radioligand, [3H]-urocortin”. Neuropharmacology. ENGLAND. 36 (10): 1439—46. ISSN 0028-3908. PMID 9423932. doi:10.1016/S0028-3908(97)00098-1.
^ Donaldson, C J; Sutton S W; et al. (1996). „Cloning and characterization of human urocortin”. Endocrinology. UNITED STATES. 137 (5): 2167—70. ISSN 0013-7227. PMID 8612563. doi:10.1210/en.137.5.2167.

Literatura

Taché Y, Martinez V, Wang L, Million M (2004). „CRF1 receptor signaling pathways are involved in stress-related alterations of colonic function and viscerosensitivity: implications for irritable bowel syndrome.”. Br. J. Pharmacol. 141 (8): 1321—30. PMC 1574904 . PMID 15100165. doi:10.1038/sj.bjp.0705760.
McLean M; Bisits A; Davies J; et al. (1995). „A placental clock controlling the length of human pregnancy.”. Nat. Med. 1 (5): 460—3. PMID 7585095. doi:10.1038/nm0595-460.
Polymeropoulos MH; Torres R; Yanovski JA; et al. (1995). „The human corticotropin-releasing factor receptor (CRHR) gene maps to chromosome 17q12-q22.”. Genomics. 28 (1): 123—4. PMID 7590738. doi:10.1006/geno.1995.1118.
Chen R, Lewis KA, Perrin MH, Vale WW (1993). „Expression cloning of a human corticotropin-releasing-factor receptor.”. Proc. Natl. Acad. Sci. U.S.A. 90 (19): 8967—71. PMC 47482 . PMID 7692441. doi:10.1073/pnas.90.19.8967.
Ross PC, Kostas CM, Ramabhadran TV (1995). „A variant of the human corticotropin-releasing factor (CRF) receptor: cloning, expression and pharmacology.”. Biochem. Biophys. Res. Commun. 205 (3): 1836—42. PMID 7811272. doi:10.1006/bbrc.1994.2884.
Opdenakker G; Fiten P; Nys G; et al. (1994). „The human MCP-3 gene (SCYA7): cloning, sequence analysis, and assignment to the C-C chemokine gene cluster on chromosome 17q11.2-q12.”. Genomics. 21 (2): 403—8. PMID 7916328. doi:10.1006/geno.1994.1283.
Vita N; Laurent P; Lefort S; et al. (1993). „Primary structure and functional expression of mouse pituitary and human brain corticotrophin releasing factor receptors.”. FEBS Lett. 335 (1): 1—5. PMID 8243652. doi:10.1016/0014-5793(93)80427-V.
Donaldson CJ; Sutton SW; Perrin MH; et al. (1996). „Cloning and characterization of human urocortin.”. Endocrinology. 137 (5): 2167—70. PMID 8612563. doi:10.1210/en.137.5.2167.
Liaw CW; Grigoriadis DE; Lovenberg TW; et al. (1997). „Localization of ligand-binding domains of human corticotropin-releasing factor receptor: a chimeric receptor approach.”. Mol. Endocrinol. 11 (7): 980—5. PMID 9178757. doi:10.1210/me.11.7.980.
Asakura H, Zwain IH, Yen SS (1997). „Expression of genes encoding corticotropin-releasing factor (CRF), type 1 CRF receptor, and CRF-binding protein and localization of the gene products in the human ovary.”. J. Clin. Endocrinol. Metab. 82 (8): 2720—5. PMID 9253360. doi:10.1210/jc.82.8.2720.
Gottowik J; Goetschy V; Henriot S; et al. (1998). „Labelling of CRF1 and CRF2 receptors using the novel radioligand, [3H]-urocortin.”. Neuropharmacology. 36 (10): 1439—46. PMID 9423932. doi:10.1016/S0028-3908(97)00098-1.
Grammatopoulos D; Dai Y; Chen J; et al. (1998). „Human corticotropin-releasing hormone receptor: differences in subtype expression between pregnant and nonpregnant myometria.”. J. Clin. Endocrinol. Metab. 83 (7): 2539—44. PMID 9661640. doi:10.1210/jc.83.7.2539.
Sakai K; Yamada M; Horiba N; et al. (1998). „The genomic organization of the human corticotropin-releasing factor type-1 receptor.”. Gene. 219 (1-2): 125—30. PMID 9757017. doi:10.1016/S0378-1119(98)00322-9.
Grammatopoulos DK; Dai Y; Randeva HS; et al. (2000). „A novel spliced variant of the type 1 corticotropin-releasing hormone receptor with a deletion in the seventh transmembrane domain present in the human pregnant term myometrium and fetal membranes.”. Mol. Endocrinol. 13 (12): 2189—202. PMID 10598591. doi:10.1210/me.13.12.2189.
Lewis K; Li C; Perrin MH; et al. (2001). „Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor.”. Proc. Natl. Acad. Sci. U.S.A. 98 (13): 7570—5. PMC 34709 . PMID 11416224. doi:10.1073/pnas.121165198.
Perrin MH; Fischer WH; Kunitake KS; et al. (2001). „Expression, purification, and characterization of a soluble form of the first extracellular domain of the human type 1 corticotropin releasing factor receptor.”. J. Biol. Chem. 276 (34): 31528—34. PMID 11425856. doi:10.1074/jbc.M101838200.
Pisarchik A, Slominski AT (2002). „Alternative splicing of CRH-R1 receptors in human and mouse skin: identification of new variants and their differential expression.”. FASEB J. 15 (14): 2754—6. PMID 11606483. doi:10.1096/fj.01-0487fje.
Graziani G; Tentori L; Portarena I; et al. (2002). „CRH inhibits cell growth of human endometrial adenocarcinoma cells via CRH-receptor 1-mediated activation of cAMP-PKA pathway.”. Endocrinology. 143 (3): 807—13. PMID 11861501. doi:10.1210/en.143.3.807.
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. PMC 139241 . PMID 12477932. doi:10.1073/pnas.242603899.
King JS, Bishop GA (2003). „The distribution and cellular localization of CRF-R1 in the vermis of the postnatal mouse cerebellum.”. Exp. Neurol. 178 (2): 175—85. PMID 12504877. doi:10.1006/exnr.2002.8052.

Spoljašnje veze

„Corticotropin-releasing Factor Receptors: CRF₁”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Архивирано из оригинала 20. 11. 2015. г.
CRF+receptor+type+1 на US National Library of Medicine Medical Subject Headings (MeSH)

Transmembranski receptor: receptori spregnuti s G proteinom

Klasa A: Rodopsinu slični

Neurotransmiter

Adrenergički	α1 (A, B, D) • α2 (A, B, C) • β1 • β2 • β3
Purinski	Adenozinski (A1, A2A, A2B, A3) • P2Y (1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14)
Serotoninski	(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

Eikozanoidni	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

Neuropeptidni

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

Orfan	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

Orfan	GPR (56, 64, 97, 98, 110, 111, 112, 113, 114, 115, 116, 123, 124, 125, 126, 128, 133, 143, 144, 155, 157)
Drugi	Moždano specifični angiogenezni inhibitor (1, 2, 3) • Kadherin (1, 2, 3) • Kalcitonin • CALCRL • CD97 • Kortikotropin-oslobađajući hormon (1, 2) • EMR (1, 2, 3) • Glukagon (GR, GIPR, GLP1R, GLP2R) • Hormon rasta • PACAPR1 • GPR • Latrofilin (1, 2, 3, ELTD1) • Metuzalemski protein • Paratiroidni hormon (1, 2) • Sekretin • Vazoaktivni intestinalni peptid (1, 2)

Klasa C: Metabotropni
glutamat / feromon

Ukus	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	Kalcijum-detektujući receptor • GABA B (1, 2) • Glutamatni receptor (Metabotropni glutamat (1, 2, 3, 4, 5, 6, 7, 8)) • GPRC6A • GPR (156, 158, 179) • RAIG (1, 2, 3, 4) • VNR (1, 2, 3, 5)

Klasa F:
Frizzled / Zaglađeni

Uvojiti	Frizzled (1, 2, 3, 4, 5, 6, 7, 8, 9, 10)
Zaglađeni	Zaglađeni

Neuropeptidni receptori

Hormonski receptori

Hipotalamusni	CRH – FSH – LHRH – TRH – Somatostatin
Hipofizni	Vazopresin (1A, 1B, 2) – Oksitocin – LHCG – Tip I citokinski receptor (GH, Prolaktin) – TSH
Drugi	Atrijalni natriuretski faktor (NPR1, NPR2, NPR3) – Kalcitonin – Holecistokinin (A, B) – VIP

Opioidni receptori

Delta – Kapa – Mi – Sigma (1, 2) – Nociceptin

Drugi neuropeptidni receptori

Angiotenzin – Bradikinin (B1, B2) / Tahikinin (TACR1) – Kalcitoninu sličan – Galanin – GPCR neuropeptid (B/W, FF, S, Y) – Neurotenzin

Neuropeptidni ligandi

Holecistokinin

CCK_A	Agonisti: Holecistokinin • CCK-4 Antagonisti: Asperlicin • Proglumid • Lorglumid • Devazepid • Deksloksiglumid
CCK_B	Agonisti: Holecistokinin • CCK-4 • Gastrin Antagonisti: Proglumid • CI-988

CRH

CRF₁	Agonisti: Kortikotropin-oslobađajuči hormon Antagonisti: Antalarmin • CP-154,526 • Peksacerfont
CRF₂	Agonisti: Kortikotropin-oslobađajuči hormon

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	Agonisti: Melanin-koncentrirajući hormon Antagonisti: ATC-0175 • GW-803,430 • NGD-4715 • SNAP-7941 • SNAP-94847
MCH₂	Agonisti: Melanin-koncentrirajući hormon

Melanokortin

MC₁	Agonisti: alfa-MSH • Afamelanotid • Bremelanotid • Melanotan II Antagonisti: Agouti signalni peptid
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

V_1A	Agonisti: Dezmopresin • Felipresin • Ornipresin • Terlipresin • Vazopresin Antagonisti: Konivaptan • Demeklociklin • Relkovaptan
V_1B	Agonisti: Felipresin • Ornipresin • Terlipresin • Vazopresin Antagonisti: Demeklociklin • Nelivaptan
V₂	Agonisti: Dezmopresin • Ornipresin • Vazopresin Antagonisti: Konivaptan • Demeklociklin • Liksivaptan • Mozavaptan • Satavaptan • Tolvaptan