Corticotropin releasing hormone receptor 1

Corticotropin releasing hormone receptor 1
Rendering based on PDB 3EHS.
Available structures PDB 3EHS, 3EHT, 3EHU
Identifiers
Symbols	CRHR1; CRF-R; CRF-R-1; CRF-R1; CRF1; CRFR-1; CRFR1; CRH-R-1; CRH-R1; CRH-R1h; CRHR; CRHR1L; CRHR1f
External IDs	OMIM: 122561 MGI: 88498 HomoloGene: 20920 GeneCards: CRHR1 Gene
Gene Ontology Molecular function • corticotrophin-releasing factor receptor activity • peptide binding • corticotropin-releasing hormone receptor activity Cellular component • multivesicular body • trans-Golgi network • plasma membrane • plasma membrane • integral to plasma membrane • dendrite • vesicle • axon part • neuronal cell body • apical part of cell Biological process • response to hypoxia • immune response • G-protein coupled receptor protein signaling pathway • G-protein signaling, coupled to cAMP nucleotide second messenger • activation of adenylate cyclase activity by G-protein signaling pathway • activation of adenylate cyclase activity • activation of phospholipase C activity by G-protein coupled receptor protein signaling pathway coupled to IP3 second messenger • elevation of cytosolic calcium ion concentration • neuropeptide signaling pathway • female pregnancy • parturition • memory • visual learning • negative regulation of appetite • eating behavior • neuroprotection • regulation of synaptic plasticity • behavioral response to pain Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1394	12921
Ensembl	ENSG00000120088	ENSMUSG00000018634
UniProt	P34998	Q0VGH2
RefSeq (mRNA)	NM_001145146.1	NM_007762.4
RefSeq (protein)	NP_001138618.1	NP_031788.1
Location (UCSC)	Chr 17: 43.7 – 43.91 Mb	Chr 11: 103.99 – 104.04 Mb
PubMed search	[1]	[2]

Corticotropin releasing hormone receptor 1 (CRHR1) is a protein, also known as CRF₁, with the latter (CRF₁) now being the IUPHAR-recommended name.^[1] In humans, CRF₁ is encoded by the CRHR1 gene.^[2][3]

Function

The corticotropin-releasing hormone receptor binds to corticotropin-releasing hormone, a potent mediator of endocrine, autonomic, behavioral, and immune responses to stress.^[4]

CRF1 receptors in mice mediate ethanol enhancement of GABAergic synaptic transmission. ^[5]

Clinical significance

Variations in the CRHR1 gene is associated with enhanced response to inhaled corticosteroid therapy in asthma.^[6] CRF1 receptor antagonists are being actively studied as possible treatments for depression and anxiety.^[7][8]

Interactions

Corticotropin releasing hormone receptor 1 has been shown to interact with Corticotropin-releasing hormone^[9][10] and Urocortin.^[11][10]

See also

• Corticotropin releasing hormone
• Corticotropin releasing hormone receptor
• Corticotropin releasing hormone antagonists
• Antalarmin
• Pexacerfont

References

1. ^ Hauger RL, Grigoriadis DE, Dallman MF, Plotsky PM, Vale WW, Dautzenberg FM (March 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. doi:10.1124/pr.55.1.3. PMID 12615952. 
2. ^ Polymeropoulos MH, Torres R, Yanovski JA, Chandrasekharappa SC, Ledbetter DH (July 1995). "The human corticotropin-releasing factor receptor (CRHR) gene maps to chromosome 17q12-q22". Genomics 28 (1): 123–4. doi:10.1006/geno.1995.1118. PMID 7590738. 
3. ^ Chen R, Lewis KA, Perrin MH, Vale WW (October 1993). "Expression cloning of a human corticotropin-releasing-factor receptor". Proc. Natl. Acad. Sci. U.S.A. 90 (19): 8967–71. doi:10.1073/pnas.90.19.8967. PMC 47482. PMID 7692441. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=47482. 
4. ^ "Entrez Gene: CRHR1 corticotropin releasing hormone receptor 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1394. 
5. ^ Nie Z, Schweitzer P, Roberts AJ, Madamba SG, Moore SD, Siggins GR (March 2004). "Ethanol augments GABAergic transmission in the central amygdala via CRF1 receptors". Science 303 (5663): 1512–4. doi:10.1126/science.1092550. PMID 15001778. 
6. ^ 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 (July 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. doi:10.1093/hmg/ddh149. PMID 15128701. 
7. ^ Kehne JH (June 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. doi:10.2174/187152707780619344. PMID 17511614. 
8. ^ Ising M, Holsboer F (December 2007). "CRH-sub-1 receptor antagonists for the treatment of depression and anxiety". Exp Clin Psychopharmacol 15 (6): 519–28. doi:10.1037/1064-1297.15.6.519. PMID 18179304. 
9. ^ Grammatopoulos, D K; Dai Y, Randeva H S, Levine M A, Karteris E, Easton A J, Hillhouse E W (Dec. 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. doi:10.1210/me.13.12.2189. ISSN 0888-8809. PMID 10598591. 
10. ^ ^{a b} Gottowik, J; Goetschy V, Henriot S, Kitas E, Fluhman B, Clerc R G, Moreau J L, Monsma F J, Kilpatrick G J (Oct. 1997). "Labelling of CRF1 and CRF2 receptors using the novel radioligand, [3H]-urocortin". Neuropharmacology (ENGLAND) 36 (10): 1439–46. doi:10.1016/S0028-3908(97)00098-1. ISSN 0028-3908. PMID 9423932. 
11. ^ Donaldson, C J; Sutton S W, Perrin M H, Corrigan A Z, Lewis K A, Rivier J E, Vaughan J M, Vale W W (May. 1996). "Cloning and characterization of human urocortin". Endocrinology (UNITED STATES) 137 (5): 2167–70. doi:10.1210/en.137.5.2167. ISSN 0013-7227. PMID 8612563. 

Further reading

• 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. doi:10.1038/sj.bjp.0705760. PMC 1574904. PMID 15100165. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1574904. 
• McLean M, Bisits A, Davies J, et al. (1995). "A placental clock controlling the length of human pregnancy". Nat. Med. 1 (5): 460–3. doi:10.1038/nm0595-460. PMID 7585095. 
• 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. doi:10.1006/geno.1995.1118. PMID 7590738. 
• 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. doi:10.1073/pnas.90.19.8967. PMC 47482. PMID 7692441. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=47482. 
• 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. doi:10.1006/bbrc.1994.2884. PMID 7811272. 
• 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. doi:10.1006/geno.1994.1283. PMID 7916328. 
• 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. doi:10.1016/0014-5793(93)80427-V. PMID 8243652. 
• Donaldson CJ, Sutton SW, Perrin MH, et al. (1996). "Cloning and characterization of human urocortin". Endocrinology 137 (5): 2167–70. doi:10.1210/en.137.5.2167. PMID 8612563. 
• 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. doi:10.1210/me.11.7.980. PMID 9178757. 
• 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. doi:10.1210/jc.82.8.2720. PMID 9253360. 
• 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. doi:10.1016/S0028-3908(97)00098-1. PMID 9423932. 
• 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. doi:10.1210/jc.83.7.2539. PMID 9661640. 
• 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. doi:10.1016/S0378-1119(98)00322-9. PMID 9757017. 
• 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. doi:10.1210/me.13.12.2189. PMID 10598591. 
• 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. doi:10.1073/pnas.121165198. PMC 34709. PMID 11416224. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=34709. 
• 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. doi:10.1074/jbc.M101838200. PMID 11425856. 
• 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. doi:10.1096/fj.01-0487fje. PMID 11606483. 
• 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. doi:10.1210/en.143.3.807. PMID 11861501. 
• 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• 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. doi:10.1006/exnr.2002.8052. PMID 12504877. 

External links

• IUPHAR GPCR Database - Corticotropin-releasing factor receptors
• "Corticotropin-releasing Factor Receptors: CRF₁". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2914. 
• MeSH Corticotropin-releasing+hormone+receptors
• MeSH CRF+receptor+type+1

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