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Gene Review

UCN3  -  urocortin 3

Homo sapiens

Synonyms: SCP, SPC, Stresscopin, UCNIII, Ucn III, ...
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Disease relevance of UCN3


Psychiatry related information on UCN3


High impact information on UCN3

  • Mouse urocortin III mRNA expression is found in areas of the brain including the hypothalamus, amygdala, and brainstem, but is not evident in the cerebellum, pituitary, or cerebral cortex; it is also expressed peripherally in small intestine and skin [7].
  • Consistent with being the only SPC subunit with at least one intrachain disulfide bond, SPC 25 contains 4 Cys residues [8].
  • AIMS: To investigate the haemodynamic, hormonal, and renal effects of peripheral urocortin 3 (Ucn3) administration for the first time in either normal health or heart failure (HF) [9].
  • Immunohistochemistry in serial tissue sections with mirror images revealed that both Ucn3 and CRF2 were colocalized in more than 85% of the adrenocortical cells. mRNA in situ hybridization confirmed these findings above [4].
  • CONCLUSIONS: Ucn1, Ucn3, and CRF receptors are all expressed in human adrenal cortex and medulla and may play important roles in physiological adrenal functions [4].

Chemical compound and disease context of UCN3


Biological context of UCN3

  • Thus SCP and SRP might represent endogenous ligands for maintaining homeostasis after stress, and could allow the design of drugs to ameliorate stress-related diseases [1].
  • Thus, a complete inventory of CRF family ligands and their receptors in the genomes of different organisms provides an opportunity to reveal an integrated view of the physiology and pathophysiology of the CRF/SCP family peptides, and offers new insights into the evolution of stress regulation in vertebrates [11].
  • The SFD associated promoter SNPs caused a gain/loss of 12 potential transcription regulatory binding sites, while the IMCL associated coding SNPs affected the secondary structure of UCN3 mRNA [3].
  • Up-regulation of nitric oxide synthase and modulation of the guanylate cyclase activity by corticotropin-releasing hormone but not urocortin II or urocortin III in cultured human pregnant myometrial cells [12].
  • Here, we investigated the effect of intracerebroventricular (ICV) injection of 0.25, 0.75, 1.50 or 3nmol/rat of Ucn II or Ucn III on food and water intake in food deprived rats [13].

Anatomical context of UCN3


Associations of UCN3 with chemical compounds

  • Ucn III secretion from the cells was measured using a highly specific RIA, and we found that high potassium, forskolin, or high glucose can stimulate Ucn III secretion from these cells [18].
  • The progress of PKC inhibitors currently in clinical development, including LY333531, ISIS 3521 (CGP 64128A), bryostatin 1, GF109203x, Ro 32-0432 and Ro 31-8220, Go 6976 and Go 7611, CPR 1006, and balanol (SPC 100840) are discussed [19].
  • The secreted rSPE B/SCP induced histamine release and degranulation of the human mast cell line HMC-1 [20].
  • We showed that the recombinant streptococcal pyogenic exotoxin B/streptococcal cysteine protease (rSPE B/SCP) was secreted into the culture supernatant of the transformant and retained its SCP activity, which was equivalent to or greater than that of the naturally occurring molecule [20].
  • This strategy of endocytic drug delivery has implications for modulating SPC protease activity needed for hormone, toxin and viral glycoprotein precursor processing in human cells [21].

Other interactions of UCN3

  • More importantly, we demonstrate that SCP and SRP are able to protect cardiomyocytes even if they are administered after the hypoxic insult and prior to reoxygenation [2].
  • Each of these four genes is highly conserved during evolution and the identity between mammalian and teleost orthologs ranges from >96% for CRF to >55% for SCP [11].
  • Cross Species Association Examination of UCN3 and CRHR2 as Potential Pharmacological Targets for Antiobesity Drugs [3].
  • Pretreatment with N/OFQ (0.25-2.0nmol/rat) did not block the effects of Ucn II and UCNIII [13].

Analytical, diagnostic and therapeutic context of UCN3

  • Furthermore, SCP and SRP protect cardiomyocytes better than UCN at concentrations up to and including 10(-10) M and reduced the amount of TUNEL positive cells almost by half at concentrations of 10(-12) to 10(-10) M [2].
  • RT-PCR showed expression of Ucn III mRNA in the brain, pituitary, heart, and kidney [14].
  • Material eluting in the position of SCP was also found in the HPLC analysis of these tissue extracts [14].
  • In the present study, we studied expression of Ucn3/SCP in the normal adrenal and adrenal tumors by radioimmunoassay and reverse transcriptase-polymerase chain reaction (RT-PCR) [5].
  • OBJECTIVE: To determine the potential benefits of ISC (intermittent self-catheterisation) over SPC (supra-pubic catheterisation) in the post-operative bladder care of women following radical hysterectomy [22].


  1. Human stresscopin and stresscopin-related peptide are selective ligands for the type 2 corticotropin-releasing hormone receptor. Hsu, S.Y., Hsueh, A.J. Nat. Med. (2001) [Pubmed]
  2. Protective effects of the urocortin homologues stresscopin (SCP) and stresscopin-related peptide (SRP) against hypoxia/reoxygenation injury in rat neonatal cardiomyocytes. Chanalaris, A., Lawrence, K.M., Stephanou, A., Knight, R.D., Hsu, S.Y., Hsueh, A.J., Latchman, D.S. J. Mol. Cell. Cardiol. (2003) [Pubmed]
  3. Cross Species Association Examination of UCN3 and CRHR2 as Potential Pharmacological Targets for Antiobesity Drugs. Jiang, Z., Michal, J.J., Williams, G.A., Daniels, T.F., Kunej, T. PLoS ONE (2006) [Pubmed]
  4. Urocortin 1, urocortin 3/stresscopin, and corticotropin-releasing factor receptors in human adrenal and its disorders. Fukuda, T., Takahashi, K., Suzuki, T., Saruta, M., Watanabe, M., Nakata, T., Sasano, H. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  5. Expression of urocortin 3/stresscopin in human adrenal glands and adrenal tumors. Takahashi, K., Totsune, K., Saruta, M., Fukuda, T., Suzuki, T., Hirose, T., Imai, Y., Sasano, H., Murakami, O. Peptides (2006) [Pubmed]
  6. Spiritual beliefs and barriers among managed care practitioners. McCauley, J., Jenckes, M.W., Tarpley, M.J., Koenig, H.G., Yanek, L.R., Becker, D.M. Journal of religion and health. (2005) [Pubmed]
  7. Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor. Lewis, K., Li, C., Perrin, M.H., Blount, A., Kunitake, K., Donaldson, C., Vaughan, J., Reyes, T.M., Gulyas, J., Fischer, W., Bilezikjian, L., Rivier, J., Sawchenko, P.E., Vale, W.W. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  8. cDNA-derived primary structure of the 25-kDa subunit of canine microsomal signal peptidase complex. Greenburg, G., Blobel, G. J. Biol. Chem. (1994) [Pubmed]
  9. Urocortin 3: haemodynamic, hormonal, and renal effects in experimental heart failure. Rademaker, M.T., Cameron, V.A., Charles, C.J., Richards, A.M. Eur. Heart J. (2006) [Pubmed]
  10. Studies of recombinant streptococcal pyrogenic exotoxin B/cysteine protease (rSPE B/SCP) in the skin of guinea pigs & the release of histamine from cultured mast cells & basophilic leukocytes. Ohkuni, H., Todome, Y., Watanabe, Y., Ishikaw, T., Takahashi, H., Kannari, Y., Kato, H., Uchiyama, T., Saito, H., Fischetti, V.A., Zabriskie, J.B. Indian J. Med. Res. (2004) [Pubmed]
  11. Ancient evolution of stress-regulating peptides in vertebrates. Chang, C.L., Hsu, S.Y. Peptides (2004) [Pubmed]
  12. Up-regulation of nitric oxide synthase and modulation of the guanylate cyclase activity by corticotropin-releasing hormone but not urocortin II or urocortin III in cultured human pregnant myometrial cells. Aggelidou, E., Hillhouse, E.W., Grammatopoulos, D.K. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  13. Activation of the Nociceptin/Orphanin FQ system is unable to reverse CRF(2) receptor mediated anorexia in the rat. Fedeli, A., Policani, F., Ubaldi, M., Cippitelli, A., Massi, M., Ciccocioppo, R. Peptides (2006) [Pubmed]
  14. Expression of urocortin III/stresscopin in human heart and kidney. Takahashi, K., Totsune, K., Murakami, O., Saruta, M., Nakabayashi, M., Suzuki, T., Sasano, H., Shibahara, S. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  15. Urocortin 3/stresscopin in human colon: possible modulators of gastrointestinal function during stressful conditions. Saruta, M., Takahashi, K., Suzuki, T., Fukuda, T., Torii, A., Sasano, H. Peptides (2005) [Pubmed]
  16. Urocortin III-immunoreactive projections in rat brain: partial overlap with sites of type 2 corticotrophin-releasing factor receptor expression. Li, C., Vaughan, J., Sawchenko, P.E., Vale, W.W. J. Neurosci. (2002) [Pubmed]
  17. Human endometrium expresses urocortin II and III messenger RNA and peptides. Florio, P., Torres, P.B., Torricelli, M., Toti, P., Vale, W., Petraglia, F. Fertil. Steril. (2006) [Pubmed]
  18. Urocortin III is expressed in pancreatic beta-cells and stimulates insulin and glucagon secretion. Li, C., Chen, P., Vaughan, J., Blount, A., Chen, A., Jamieson, P.M., Rivier, J., Smith, M.S., Vale, W. Endocrinology (2003) [Pubmed]
  19. Protein kinase C in the treatment of disease: signal transduction pathways, inhibitors, and agents in development. Goekjian, P.G., Jirousek, M.R. Current medicinal chemistry. (1999) [Pubmed]
  20. Cysteine protease activity and histamine release from the human mast cell line HMC-1 stimulated by recombinant streptococcal pyrogenic exotoxin B/streptococcal cysteine protease. Watanabe, Y., Todome, Y., Ohkuni, H., Sakurada, S., Ishikawa, T., Yutsudo, T., Fischetti, V.A., Zabriskie, J.B. Infect. Immun. (2002) [Pubmed]
  21. Endocytic delivery of intramolecularly quenched substrates and inhibitors to the intracellular yeast Kex2 protease1. Henkel, M.K., Pott, G., Henkel, A.W., Juliano, L., Kam, C.M., Powers, J.C., Franzusoff, A. Biochem. J. (1999) [Pubmed]
  22. A prospective randomised controlled trial of intermittent self-catheterisation vs. supra-pubic catheterisation for post-operative bladder care following radical hysterectomy. Naik, R., Maughan, K., Nordin, A., Lopes, A., Godfrey, K.A., Hatem, M.H. Gynecol. Oncol. (2005) [Pubmed]
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