Corticotropin-releasing hormone receptor 1

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Corticotropin releasing hormone receptor 1
Protein CRHR1 PDB 3EHS.png
Rendering based on PDB 3EHS.
Available structures
PDB Ortholog search: PDBe, RCSB
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 OMIM122561 MGI88498 HomoloGene20920 IUPHAR: CRF1 ChEMBL: 1800 GeneCards: CRHR1 Gene
RNA expression pattern
PBB GE CRHR1 214619 at tn.png
PBB GE CRHR1 208593 x at tn.png
PBB GE CRHR1 211897 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 1394 12921
Ensembl ENSG00000120088 ENSMUSG00000018634
UniProt P34998 P35347
RefSeq (mRNA) NM_001145146 NM_007762
RefSeq (protein) NP_001138618 NP_031788
Location (UCSC) Chr 17:
43.7 – 43.91 Mb
Chr 11:
104.13 – 104.18 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[edit]

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]

Evolution[edit]

Corticotrophin releasing hormone (CRH) evolved ~500 million years ago in an organism that subsequently gave rise to both chordates and arthropods.[6] The binding site for this was single CRH like receptor. In vertebrates this gene was duplicated leading to the extant CRH1 and CRH2 forms. Additionally four paralogous ligands developed including CRH, urotenin-1/urocortin, urocortin 2 and urocortin 3.

Clinical significance[edit]

Variations in the CRHR1 gene is associated with enhanced response to inhaled corticosteroid therapy in asthma.[7]

CRF1 triggers cells to release hormones that are linked to stress and anxiety.[8] Hence CRF1 receptor antagonists are being actively studied as possible treatments for depression and anxiety.[9][10]

Interactions[edit]

Corticotropin-releasing hormone receptor 1 has been shown to interact with Corticotropin-releasing hormone[11][12] and Urocortin.[13]

See also[edit]

References[edit]

  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. 
  4. ^ "Entrez Gene: CRHR1 corticotropin releasing hormone receptor 1". 
  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. ^ Lovejoy D, Chang B, Lovejoy N, Del Castillo J (2014) Origin and functional evolution of the corticotrophin-releasing hormone receptors. J Mol Endocrinol
  7. ^ 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. 
  8. ^ Hollenstein K, Kean J, Bortolato A, Cheng RK, Doré AS, Jazayeri A, Cooke RM, Weir M, Marshall FH (July 2013). "Structure of class B GPCR corticotropin-releasing factor receptor 1". Nature 499 (7459): 438–43. doi:10.1038/nature12357. PMID 23863939. 
  9. ^ 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. 
  10. ^ 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. 
  11. ^ Grammatopoulos DK, Dai Y, Randeva HS, Levine MA, Karteris E, Easton AJ, Hillhouse EW (December 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. 13 (12): 2189–202. doi:10.1210/me.13.12.2189. PMID 10598591. 
  12. ^ Gottowik J, Goetschy V, Henriot S, Kitas E, Fluhman B, Clerc RG, Moreau JL, Monsma FJ, Kilpatrick GJ (October 1997). "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. 
  13. ^ Donaldson CJ, Sutton SW, Perrin MH, Corrigan AZ, Lewis KA, Rivier JE, Vaughan JM, Vale WW (May 1996). "Cloning and characterization of human urocortin". Endocrinology 137 (5): 2167–70. doi:10.1210/en.137.5.2167. PMID 8612563. 


Further reading[edit]

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.