The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Ucn  -  urocortin

Rattus norvegicus

Synonyms: Corticotensin, Urocortin
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Ucn


Psychiatry related information on Ucn


High impact information on Ucn

  • Synthetic urocortin evokes secretion of adrenocorticotropic hormone (ACTH) both in vitro and in vivo and binds and activates transfected type-1 CRF receptors, the subtype expressed by pituitary corticotropes [10].
  • In this issue of the JCI, McCrimmon and colleagues report that application of urocortin I (a corticotrophin-releasing factor receptor-2 agonist) to the ventromedial hypothalamus reduces the glucose counterregulatory response to hypoglycemia in rats (see the related article beginning on page 1723) [11].
  • Thus, hypothalamic urocortin I release during antecedent hypoglycemia is, among other possibilities, a potential mechanism of HAAF [11].
  • In the gastrointestinal tract, CRF actions are largely proinflammatory, whereas the effects of the Ucn subtypes can be either pro- or antiinflammatory [12].
  • Urocortin protects against ischemic and reperfusion injury via a MAPK-dependent pathway [13].

Chemical compound and disease context of Ucn


Biological context of Ucn

  • In the present study, we investigated Ucn effects on IL-6 gene expression and IL-6 synthesis in A7r5 aortic smooth muscle cells [17].
  • The intracisternal injection of Ucn 2 (0.1 and 1 microg) and Ucn 1 (1 microg) decreased gastric emptying to 37.8 +/- 6.9%, 23.1 +/- 8.6%, and 21.6 +/- 5.9%, respectively, compared with 58.4 +/- 3.8% after intracisternal vehicle [18].
  • It is concluded that Ucn, at doses that reduce food intake to levels like that observed after administration of CRH, do not produce similarly aversive consequences [19].
  • CRF receptor antagonist diminished both coronary vasodilation and the positive inotropic effects of Ucn (P<0.05) [20].
  • Urocortin has been implicated in various endocrine responses, such as blood pressure regulation, as well as in higher cognitive functions [21].

Anatomical context of Ucn


Associations of Ucn with chemical compounds

  • The adenylate cyclase inhibitor, MDL-12330A, inhibited this Ucn- or Ucn II-induced increase in IL-6 levels [23].
  • Indomethacin significantly attenuated the vasodilator effects of Ucn (P<0.05) [20].
  • The effects of Ucn were then analyzed to determine whether these effects were mediated by CRF receptors and/or any other mediators under the following conditions: perfusion buffer containing (1) alpha-helical CRF 9-41, (2) indomethacin, (3) N(G)-nitro-l -arginine methylester and (4) propranolol [20].
  • The performance-enhancing effects of Ucn in both water maze and passive avoidance paradigms were reversed by i.c.v. pretreatment with D-Phe CRF(12-41) (2.5, 5 microg), a broad CRF(1)/CRF(2) receptor antagonist, or antalarmin (10 microg), a potent, nonpeptide, CRF(1) selective receptor antagonist [24].
  • This switch in polarity of Ucn I-mediated neuromodulation, from a negative to positive regulation of excitatory glutamatergic transmission after chronic cocaine administration, could generate an imbalance in the brain reward circuitry associated with the LSMLN [25].

Physical interactions of Ucn

  • Urocortin (Ucn) is a closely related mammalian peptide that binds to both identified CRH receptor subtypes and also reduces food intake when administered i3vt [19].
  • A chimera in which both the first and fourth extracellular domains of the CRF-R1 replaced the corresponding domains of the GRF-R bound astressin with Ki approximately 4 nM and urocortin with a Ki approximately 2 nM [26].
  • The mature peptide is rapidly released, and exerts autocrine/paracrine protective effects through the cardiac CRH-R2 receptor which preferentially binds urocortin [27].

Regulatory relationships of Ucn

  • These results identify urocortin as a novel hypertrophic and protective agent whose hypertrophic effect is mediated by a distinct pathway to that activated by CT-1, although the two factors mediate protection via the same pathway [1].
  • The results suggest that urocortin induces relaxation of cerebral arteries by activating CRF-R2 receptors present in the vascular wall [28].
  • These results demonstrate that the increase in the expression of CRF and urocortin message in magnocellular neurones induced by salt loading is accompanied by an increase in CRF receptor levels and binding in the hypothalamus and intermediate pituitary [29].
  • Ucn also enhanced endothelin-1-induced increase of [(3)H]-thymidine uptake into NMCs [3].
  • This Ucn-induced plasticity appears to be dependent on NMDA receptor and subsequent calcium-calmodulin-dependent protein kinase II (CaMKII) activation, because it is blocked by pretreatment with NMDA receptor antagonists and by coadministration of CaMKII inhibitors [30].

Other interactions of Ucn

  • Experiment 1 found that 1.0 microg Ucn and 2.0 microg CRH produced similar reductions in food intake [19].
  • The hypertrophic effect of CT-1 was dependent on the signal transducer and activator of transcription 3 (STAT3) pathway but the hypertrophic effect of urocortin was independent of this pathway [1].
  • Using subtype-selective CRH receptor antagonists, we provide evidence that the neuroprotective effect of exogenously added urocortin is mediated by CRHR1 [31].
  • Therefore, we mapped local mRNA and peptide/protein presence of both Ucn and the NO producing neuronal NO synthase (nNOS) [22].
  • Urocortin-related peptides increase interleukin-6 output via cyclic adenosine 5'-monophosphate-dependent pathways in A7r5 aortic smooth muscle cells [23].

Analytical, diagnostic and therapeutic context of Ucn


  1. Cardiotrophin-1 and urocortin cause protection by the same pathway and hypertrophy via distinct pathways in cardiac myocytes. Railson, J.E., Liao, Z., Brar, B.K., Buddle, J.C., Pennica, D., Stephanou, A., Latchman, D.S. Cytokine (2002) [Pubmed]
  2. Urocortin and inflammation: confounding effects of hypotension on measures of inflammation. Torpy, D.J., Webster, E.L., Zachman, E.K., Aguilera, G., Chrousos, G.P. Neuroimmunomodulation (1999) [Pubmed]
  3. Urocortin has cell-proliferative effects on cardiac non-myocytes. Ikeda, K., Tojo, K., Oki, Y., Nakao, K. Life Sci. (2002) [Pubmed]
  4. Stress and autoimmunity: the neuropeptides corticotropin-releasing factor and urocortin suppress encephalomyelitis via effects on both the hypothalamic-pituitary-adrenal axis and the immune system. Poliak, S., Mor, F., Conlon, P., Wong, T., Ling, N., Rivier, J., Vale, W., Steinman, L. J. Immunol. (1997) [Pubmed]
  5. The role of neuropeptide Y in the amygdala on corticotropin-releasing factor receptor-mediated behavioral stress responses in the rat. Sajdyk, T.J., Fitz, S.D., Shekhar, A. Stress (Amsterdam, Netherlands) (2006) [Pubmed]
  6. The postnatal developmental expression pattern of urocortin in the rat olivocerebellar system. Swinny, J.D., Kalicharan, D., Brouwer, N., Biber, K., Shi, F., Gramsbergen, A., van der Want, J.J. J. Comp. Neurol. (2004) [Pubmed]
  7. Down-regulation of corticotropin-releasing hormone receptor type 2beta mRNA expression in the rat cardiovascular system following food deprivation. Nazarloo, H.P., Nishiyama, M., Tanaka, Y., Asaba, K., Hashimoto, K. Regul. Pept. (2002) [Pubmed]
  8. Neurons colocalizing urocortin and cocaine and amphetamine-regulated transcript immunoreactivities are induced by acute lipopolysaccharide stress in the Edinger-Westphal nucleus in the rat. Kozicz, T. Neuroscience (2003) [Pubmed]
  9. Stress and central Urocortin increase anxiety-like behavior in the social interaction test via the CRF1 receptor. Gehlert, D.R., Shekhar, A., Morin, S.M., Hipskind, P.A., Zink, C., Gackenheimer, S.L., Shaw, J., Fitz, S.D., Sajdyk, T.J. Eur. J. Pharmacol. (2005) [Pubmed]
  10. Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor. Vaughan, J., Donaldson, C., Bittencourt, J., Perrin, M.H., Lewis, K., Sutton, S., Chan, R., Turnbull, A.V., Lovejoy, D., Rivier, C. Nature (1995) [Pubmed]
  11. Mechanisms of sympathoadrenal failure and hypoglycemia in diabetes. Cryer, P.E. J. Clin. Invest. (2006) [Pubmed]
  12. Role of peripheral corticotropin-releasing factor and urocortin II in intestinal inflammation and motility in terminal ileum. la Fleur, S.E., Wick, E.C., Idumalla, P.S., Grady, E.F., Bhargava, A. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  13. Urocortin protects against ischemic and reperfusion injury via a MAPK-dependent pathway. Brar, B.K., Jonassen, A.K., Stephanou, A., Santilli, G., Railson, J., Knight, R.A., Yellon, D.M., Latchman, D.S. J. Biol. Chem. (2000) [Pubmed]
  14. Cardioprotective action of CRF peptide urocortin against simulated ischemia in adult rat cardiomyocytes. Gordon, J.M., Dusting, G.J., Woodman, O.L., Ritchie, R.H. Am. J. Physiol. Heart Circ. Physiol. (2003) [Pubmed]
  15. Urocortinergic neurons respond in a differentiated manner to various acute stressors in the Edinger-Westphal nucleus in the rat. Gaszner, B., Csernus, V., Kozicz, T. J. Comp. Neurol. (2004) [Pubmed]
  16. Long-term effects on feeding and body weight after stimulation of forebrain or hindbrain CRH receptors with urocortin. Grill, H.J., Markison, S., Ginsberg, A., Kaplan, J.M. Brain Res. (2000) [Pubmed]
  17. Urocortin induces interleukin-6 gene expression via cyclooxygenase-2 activity in aortic smooth muscle cells. Kageyama, K., Hanada, K., Nigawara, T., Moriyama, T., Terui, K., Sakihara, S., Suda, T. Endocrinology (2006) [Pubmed]
  18. Urocortin 2 acts centrally to delay gastric emptying through sympathetic pathways while CRF and urocortin 1 inhibitory actions are vagal dependent in rats. Czimmer, J., Million, M., Taché, Y. Am. J. Physiol. Gastrointest. Liver Physiol. (2006) [Pubmed]
  19. Comparison of central administration of corticotropin-releasing hormone and urocortin on food intake, conditioned taste aversion, and c-Fos expression. Benoit, S.C., Thiele, T.E., Heinrichs, S.C., Rushing, P.A., Blake, K.A., Steeley, R.J. Peptides (2000) [Pubmed]
  20. Coronary vasodilation and positive inotropism by urocortin in the isolated rat heart. Terui, K., Higashiyama, A., Horiba, N., Furukawa, K.I., Motomura, S., Suda, T. J. Endocrinol. (2001) [Pubmed]
  21. Distribution of urocortin-like immunoreactivity in the central nervous system of the rat. Kozicz, T., Yanaihara, H., Arimura, A. J. Comp. Neurol. (1998) [Pubmed]
  22. Colocalization of urocortin and neuronal nitric oxide synthase in the hypothalamus and Edinger-Westphal nucleus of the rat. Spina, M.G., Langnaese, K., Orlando, G.F., Horn, T.F., Rivier, J., Vale, W.W., Wolf, G., Engelmann, M. J. Comp. Neurol. (2004) [Pubmed]
  23. Urocortin-related peptides increase interleukin-6 output via cyclic adenosine 5'-monophosphate-dependent pathways in A7r5 aortic smooth muscle cells. Kageyama, K., Suda, T. Endocrinology (2003) [Pubmed]
  24. Urocortin shares the memory modulating effects of corticotropin-releasing factor (CRF): mediation by CRF1 receptors. Zorrilla, E.P., Schulteis, G., Ormsby, A., Klaassen, A., Ling, N., McCarthy, J.R., Koob, G.F., De Souza, E.B. Brain Res. (2002) [Pubmed]
  25. Chronic cocaine administration switches corticotropin-releasing factor2 receptor-mediated depression to facilitation of glutamatergic transmission in the lateral septum. Liu, J., Yu, B., Orozco-Cabal, L., Grigoriadis, D.E., Rivier, J., Vale, W.W., Shinnick-Gallagher, P., Gallagher, J.P. J. Neurosci. (2005) [Pubmed]
  26. The first extracellular domain of corticotropin releasing factor-R1 contains major binding determinants for urocortin and astressin. Perrin, M.H., Sutton, S., Bain, D.L., Berggren, W.T., Vale, W.W. Endocrinology (1998) [Pubmed]
  27. CRH-like peptides protect cardiac myocytes from lethal ischaemic injury. Brar, B.K., Stephanou, A., Okosi, A., Lawrence, K.M., Knight, R.A., Marber, M.S., Latchman, D.S. Mol. Cell. Endocrinol. (1999) [Pubmed]
  28. Characterization of the relaxant action of urocortin, a new peptide related to corticotropin-releasing factor in the rat isolated basilar artery. Schilling, L., Kanzler, C., Schmiedek, P., Ehrenreich, H. Br. J. Pharmacol. (1998) [Pubmed]
  29. Expression of corticotropin releasing factor (CRF), urocortin and CRF type 1 receptors in hypothalamic-hypophyseal systems under osmotic stimulation. Imaki, T., Katsumata, H., Miyata, M., Naruse, M., Imaki, J., Minami, S. J. Neuroendocrinol. (2001) [Pubmed]
  30. Corticotrophin releasing factor-induced synaptic plasticity in the amygdala translates stress into emotional disorders. Rainnie, D.G., Bergeron, R., Sajdyk, T.J., Patil, M., Gehlert, D.R., Shekhar, A. J. Neurosci. (2004) [Pubmed]
  31. Urocortin, but not urocortin II, protects cultured hippocampal neurons from oxidative and excitotoxic cell death via corticotropin-releasing hormone receptor type I. Pedersen, W.A., Wan, R., Zhang, P., Mattson, M.P. J. Neurosci. (2002) [Pubmed]
  32. Distribution of urocortin in the rat's gastrointestinal tract and its colocalization with tyrosine hydroxylase. Kozicz, T., Arimura, A. Peptides (2002) [Pubmed]
  33. Acute stress results in skin corticotropin-releasing hormone secretion, mast cell activation and vascular permeability, an effect mimicked by intradermal corticotropin-releasing hormone and inhibited by histamine-1 receptor antagonists. Lytinas, M., Kempuraj, D., Huang, M., Boucher, W., Esposito, P., Theoharides, T.C. Int. Arch. Allergy Immunol. (2003) [Pubmed]
  34. Cardiac inotropic actions of urocortin in conscious sheep. Parkes, D.G., Vaughan, J., Rivier, J., Vale, W., May, C.N. Am. J. Physiol. (1997) [Pubmed]
  35. Corticotropin-releasing factor but not urocortin is involved in adrenalectomy-induced adrenocorticotropin release. Masuzawa, M., Oki, Y., Ozawa, M., Watanabe, F., Yoshimi, T. J. Neuroendocrinol. (1999) [Pubmed]
WikiGenes - Universities