Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • Tarik SmaniEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101942


 Ucn-1: Ucn; Ucn I; UROC; Urocortin; Urocortin 1; Urocortin I

 Ucn-2: Ucn2; Urocortin 2; Urocortin II

 Ucn-3: SCP; SPC; Stresscopin; Ucn3; UCNIII; Urocortin 3; Urocortin III

Historical Background

In mid-nineties, urocortin (Ucn), a 40 amino acid peptide, was identified as a new member of family a highly evolutionary conserved corticotropin-releasing factor (CRF) peptide discovered earlier in 1981 (Vale et al. 1981). Vaughan and colleagues used a probe derived from urotensin, a fish member of the CRF family, and discovered immunoreactivity in localized rat midbrain region (Vaughan et al. 1995). Urocortin isoforms are widely expressed in the heart, central nervous system, gut, skeletal muscle, skin, and immune system (Davidson et al. 2009). It has several systemic actions associated with stress; it mimics some of CRF effects in the nervous system as it enhanced anxiety and is a potent suppressor of appetite and feeding behavior (Pan and Kastin 2008). Urocortin has strong...

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  1. Adão R, Santos-Ribeiro D, Rademaker MT, Leite-Moreira AF, Brás-Silva C. Urocortin 2 in cardiovascular health and disease. Drug Discov Today. 2015;20(7):906–14.  https://doi.org/10.1016/j.drudis.2015.02.012.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Baigent SM, Lowry PJ. mRNA expression profiles for corticotrophin releasing factor (CRF), urocortin, CRF receptors and CRF-binding protein in peripheral rat tissues. J Mol Endocrinol. 2000;25:43–52.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Calderon-Sanchez E, Delgado C, Ruiz-Hurtado G, Domínguez-Rodríguez A, Cachofeiro V, Rodríguez-Moyano M, Gomez AM, Ordóñez A, Smani T. Urocortin induces positive inotropic effect in rat heart. Cardiovasc Res. 2009;83:717–25.  https://doi.org/10.1093/cvr/cvp161.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Calderón-Sánchez E, Díaz I, Ordóñez A, Smani T. Urocortin-1 mediated cardioprotection involves XIAP and CD40-ligand recovery: role of EPAC2 and ERK1/2. PLoS One. 2016;11(2):e0147375.  https://doi.org/10.1371/journal.pone.0147375.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Chen A, Blount A, Vaughan J, Brar B, Vale W. Urocortin II gene is highly expressed in mouse skin and skeletal muscle tissues: localization, basal expression in CRF1 and CRF2-null mice and regulation by glucocorticoids. Endocrinology. 2004;145:2445–57.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Dautzenberg FM, Hauger RL. The CRF peptide family and their receptors: yet more partners discovered. Trends Pharmacol Sci. 2002;23(2):71–7.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Davidson SM, Rybka AE, Townsend PA. The powerful cardioprotective effects of urocortin and the corticotropin releasing hormone (CRH) family. Biochem Pharmacol. 2009;77:141–50.  https://doi.org/10.1016/j.bcp.2008.08.033.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Davis ME, Pemberton CJ, Yandle TG, Fisher SF, Lainchbury JG, Frampton CM, Rademaker MT, Richards M. Urocortin 2 infusion in healthy humans: hemodynamic, neurohormonal, and renal responses. J Am Coll Cardiol. 2007;49:461–71.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Diaz I, Smani T. New insights into the mechanisms underlying vascular and cardiac effects of urocortin. Curr Vasc Pharmacol. 2013;11(4):457–64.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Donaldson CJ, Sutton SW, Perrin MH, Corrigan AZ, Lewis KA, Rivier JE, Vaughan JM, Vale WW. Cloning and characterization of human urocortin. Endocrinology. 1996 May;137(5):2167–70. Erratum in: Endocrinology. 1996 Sep;137(9):3896.Google Scholar
  11. Gao MH, Giamouridis D, Lai NC, Walenta E, Paschoal VA, Kim YC, Miyanohara A, Guo T, Liao M, Liu L, Tan Z, Ciaraldi TP, Schenk S, Bhargava A, Oh DY, Hammond HK. One-time injection of AAV8 encoding urocortin 2 provides long-term resolution of insulin resistance. JCI Insight. 2016;1(15):e88322.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Henckens MJ, Deussing JM, Chen A. Region-specific roles of the corticotropin-releasing factor-urocortin system in stress. Nat Rev Neurosci. 2016;17(10):636–51.  https://doi.org/10.1038/nrn.2016.94.CrossRefPubMedPubMedCentralGoogle Scholar
  13. Latchaman DS. Urocortin. Int J Biochem Cell Biol. 2002;34(8):907–10.CrossRefGoogle Scholar
  14. Lawrence KM, Scarabelli TM, Turtle L, Chanalaris A, Townsend PA, Carroll CJ, Hubank M, Stephanou A, Knight RA, Latchman DS. Urocortin protects cardiac myocytes from ischemia/reperfusión injury by attenuating calcium-sensitive phospholipase A2 gene expression. FASEB J. 2003;17:2313–5.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Neufeld-Cohen A, Tsoory MM, Evans AK, Getselter D, Gil S, Lowry CA, Vale WW, Chen A. A triple urocortin knockout mouse model reveals an essential role for urocortins in stress recovery. Proc Natl Acad Sci USA. 2010;107(44):19020–5.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Pan W, Kastin AJ. Urocortin and the brain. Prog Neurobiol. 2008;84(2):148–56.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Reutenauer-Patte J, Boittin FX, Patthey-Vuadens O, Ruegg UT, Dorchies OM. Urocortins improve dystrophic skeletal muscle structure and function through both PKA- and Epac-dependent pathways. Am J Pathol. 2012;180(2):749–62.  https://doi.org/10.1016/j.ajpath.2011.10.038.CrossRefPubMedPubMedCentralGoogle Scholar
  18. Smani T, Calderon E, Rodriguez-Moyano M, Dominguez-Rodriguez A, Diaz I, Ordóñez A. Urocortin-2 induces vasorelaxation of coronary arteries isolated from patients with heart failure. Clin Exp Pharmacol Physiol. 2011;38(1):71–6.  https://doi.org/10.1111/j.1440-1681.2010.05466.x.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Vale W, Spiess J, Rivier C, Rivier J. Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin. Science. 1981;213:1394–7.PubMedCrossRefGoogle Scholar
  20. Vaughan J, Donaldson C, Bittencourt J, Perrin MH, Lewis K, Sutton S, Chan R, Turnbull AV, Lovejoy D, Rivier C, Rivier J, Sawchenko PE, Vale W. Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor. Nature. 1995;378:287–92.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Wiley KE, Davenport AP. CRF2 receptors are highly expressed in the human cardiovascular system and their cognate ligands urocortins 2 and 3 are potent vasodilators. Br J Pharmacol. 2004;143:508–14.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Grupo de Fisiopatología Cardiovascular, Lab 113Instituto de Biomedicina de Sevilla/Hospital Universitario Virgen del RocíoSevillaSpain