Corticotropin-releasing factor receptors
More information on this family may be found on the IUPHAR-DB family and introduction pages.
Corticotropin-releasing factor (CRF, nomenclature as recommended by the NC-IUPHAR sub-committee on Corticotropin-releasing Factor Receptors, [7]) receptors are activated by the endogenous peptides CRF (also known as corticotropin-releasing hormone [CRH], a 41 amino-acid peptide, ENSG00000147571), urocortin 1 (a 40 amino-acid peptide, ENSG00000163794), urocortin 2 (a 38 amino-acid peptide, ENSG00000145040) and urocortin 3 (a 38 amino-acid peptide, ENSG00000178473). CRF1 and CRF2 receptors are activated non-selectively by CRF and urocortin 1. Binding to CRF receptors can be conducted using [125I]Tyr0-CRF or [125I]Tyr0-sauvagine with Kd values of 0.1–0.4 nM. CRF1 and CRF2 receptors are non-selectively antagonized by α-helical CRF, D-Phe-CRF-(12-41) and astressin.
Unless otherwise stated all data refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Receptors 
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Binder, EB; Nemeroff, CB. (2010) The CRF system, stress, depression and anxiety-insights from human genetic studies. Mol. Psychiatry, 15 (6): 574-88. [PMID:20010888]
Bonci, A; Borgland, S. (2009) Role of orexin/hypocretin and CRF in the formation of drug-dependent synaptic plasticity in the mesolimbic system. Neuropharmacology, 56 Suppl 1: 107-11. [PMID:18694770]
Fekete, EM; Zorrilla, EP. (2007) Physiology, pharmacology, and therapeutic relevance of urocortins in mammals: ancient CRF paralogs. Front Neuroendocrinol, 28 (1): 1-27. [PMID:17083971]
Hauger, R. L., Grigoriadis, D. E., Dallman, M. F., Plotsky, P. M., Vale, W. W. and Dautzenberg, F. M. (2003) International Union of Pharmacology. XXXVI. Current status of the nomenclature for receptors for corticotropin-releasing factor and their ligands. Pharmacol Rev., 55: 21-26. [PMID:12615952]
Kehne, JH; Cain, CK. (2010) Therapeutic utility of non-peptidic CRF1 receptor antagonists in anxiety, depression, and stress-related disorders: evidence from animal models. Pharmacol. Ther., 128 (3): 460-87. [PMID:20826181]
Koob, GF. (2010) The role of CRF and CRF-related peptides in the dark side of addiction. Brain Res., 1314: 3-14. [PMID:19912996]
Taché, Y; Bonaz, B. (2007) Corticotropin-releasing factor receptors and stress-related alterations of gut motor function. J. Clin. Invest., 117 (1): 33-40. [PMID:17200704]
Tsatsanis, C; Dermitzaki, E; Venihaki, M; Chatzaki, E; Minas, V; Gravanis, A; Margioris, AN. (2007) The corticotropin-releasing factor (CRF) family of peptides as local modulators of adrenal function. Cell. Mol. Life Sci., 64 (13): 1638-55. [PMID:17453142]
Wise, RA; Morales, M. (2010) A ventral tegmental CRF-glutamate-dopamine interaction in addiction. Brain Res., 1314: 38-43. [PMID:19800323]
Ziegler, CG; Krug, AW; Zouboulis, CC; Bornstein, SR. (2007) Corticotropin releasing hormone and its function in the skin. Horm. Metab. Res., 39 (2): 106-9. [PMID:17326006]
1. Chaki, S; Okuyama, S; Nakazato, A; Kumagai, T; Okubo, T; Ikeda, Y; Oshida, Y; Hamajima, Y; Tomisawa, K. (1999) In vitro pharmacological profile of nonpeptide CRF1 receptor antagonists, CRA1000 and CRA1001. Eur. J. Pharmacol., 371 (2-3): 205-11. [PMID:10357258]
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3. Chen, YL; Obach, RS; Braselton, J; Corman, ML; Forman, J; Freeman, J; Gallaschun, RJ; Mansbach, R; Schmidt, AW; Sprouse, JS; et al.. (2008) 2-aryloxy-4-alkylaminopyridines: discovery of novel corticotropin-releasing factor 1 antagonists. J. Med. Chem., 51 (5): 1385-92. [PMID:18288792]
4. Dautzenberg, F. M., Gutknecht, E., Van der Linden, I., Olivares-Reyes, J. A., Dürrenberger, F. and Hauger, R. L. (2004) Cell type specific calcium signaling by corticotropin-releasing factor type 1 (CRF1) and 2a (CRF2(a)) receptors: Gq coupling in human embryonic kidney 293 but not SK-N-MC neuroblastoma cells. Biochem Pharmacol., 68: 1833-1844. [PMID:15450949]
5. Dautzenberg, F. M., Py-Lang, G., Higelin, J., Fischer, C., Wright, M. B. and Huber, G. (2001) Different binding modes of amphibian and human corticotropin-releasing factor type 1 and type 2 receptors: evidence for evolutionary differences. J Pharmacol Exp Ther., 296: 113-120. [PMID:11123370]
6. Gully, D; Geslin, M; Serva, L; Fontaine, E; Roger, P; Lair, C; Darre, V; Marcy, C; Rouby, PE; Simiand, J; et al.. (2002) 4-(2-Chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]5-methyl-N-(2-propynyl)-1,3-thiazol-2-amine hydrochloride (SSR125543A): a potent and selective corticotrophin-releasing factor(1) receptor antagonist. I. Biochemical and pharmacological characterization. J. Pharmacol. Exp. Ther., 301 (1): 322-32. [PMID:11907190]
7. Hauger, R. L., Grigoriadis, D. E., Dallman, M. F., Plotsky, P. M., Vale, W. W. and Dautzenberg, F. M. (2003) International Union of Pharmacology. XXXVI. Current status of the nomenclature for receptors for corticotropin-releasing factor and their ligands. Pharmacol Rev., 55: 21-26. [PMID:12615952]
8. He, L; Gilligan, PJ; Zaczek, R; Fitzgerald, LW; McElroy, J; Shen, HS; Saye, JA; Kalin, NH; Shelton, S; Christ, D; et al.. (2000) 4-(1,3-Dimethoxyprop-2-ylamino)-2,7-dimethyl-8-(2, 4-dichlorophenyl)pyrazolo[1,5-a]-1,3,5-triazine: a potent, orally bioavailable CRF(1) receptor antagonist. J. Med. Chem., 43 (3): 449-56. [PMID:10669572]
9. Lawrence, AJ; Krstew, EV; Dautzenberg, FM; Rühmann, A. (2002) The highly selective CRF(2) receptor antagonist K41498 binds to presynaptic CRF(2) receptors in rat brain. Br. J. Pharmacol., 136 (6): 896-904. [PMID:12110614]
10. Lundkvist, J; Chai, Z; Teheranian, R; Hasanvan, H; Bartfai, T; Jenck, F; Widmer, U; Moreau, JL. (1996) A non peptidic corticotropin releasing factor receptor antagonist attenuates fever and exhibits anxiolytic-like activity. Eur. J. Pharmacol., 309 (2): 195-200. [PMID:8874139]
11. Perkins, AV; Wolfe, CD; Eben, F; Soothill, P; Linton, EA. (1995) Corticotrophin-releasing hormone-binding protein in human fetal plasma. J. Endocrinol., 146 (3): 395-401. [PMID:7595134]
12. Rühmann, A; Chapman, J; Higelin, J; Butscha, B; Dautzenberg, FM. (2002) Design, synthesis and pharmacological characterization of new highly selective CRF(2) antagonists: development of 123I-K31440 as a potential SPECT ligand. Peptides, 23 (3): 453-60. [PMID:11835994]
13. Webster, EL; Lewis, DB; Torpy, DJ; Zachman, EK; Rice, KC; Chrousos, GP. (1996) In vivo and in vitro characterization of antalarmin, a nonpeptide corticotropin-releasing hormone (CRH) receptor antagonist: suppression of pituitary ACTH release and peripheral inflammation. Endocrinology, 137 (12): 5747-50. [PMID:8940412]
14. Zobel, AW; Nickel, T; Künzel, HE; Ackl, N; Sonntag, A; Ising, M; Holsboer, F. (2000) Effects of the high-affinity corticotropin-releasing hormone receptor 1 antagonist R121919 in major depression: the first 20 patients treated. J Psychiatr Res, 34 (3): 171-81. [PMID:10867111]
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A CRF binding protein has been identified (CRF-BP, ENSG00000145708) to which both CRF and urocortin 1 bind with high affinities, which has been suggested to bind and inactivate circulating CRF [11].