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Chemical Compound Review

Uroguanylin     (4S)-4-[[(2S)-2-[[(2S)-2- [[(2S)-2-[[(2S)-2...

Synonyms: AC1NUQUT, 152175-68-3
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Disease relevance of Uroguanylin


High impact information on Uroguanylin


Biological context of Uroguanylin

  • Finally, telemetric recordings of blood pressure demonstrated increased mean arterial pressure in uroguanylin knockout animals that was independent of the level of dietary salt intake [5].
  • To explore the in vivo role of uroguanylin in the regulation of sodium excretion, we created gene-targeted mice in which uroguanylin gene expression had been ablated [5].
  • ST or uroguanylin inhibited proliferation of T84 and Caco2 cells, but not SW480 cells, in a concentration-dependent fashion, assessed by quantifying cell number, cell protein, and [(3)H]thymidine incorporation into DNA [6].
  • High mucosal acidity, similar to the pH occurring within the fluid microclimate domain at the mucosal surface of the intestine, markedly enhances the cGMP accumulation responses of T84 human intestinal cells to uroguanylin [7].
  • For uroguanylin two distinct signaling pathways exist in IHKE-1 cells, one involves GC-C and cGMP as second messenger, the other is cGMP-independent and connected to a pertussis toxin-sensitive G protein [3].

Anatomical context of Uroguanylin


Associations of Uroguanylin with other chemical compounds


Gene context of Uroguanylin

  • Uroguanylin expression was significantly lower in GC-C-/- mice than in GC-A-/- and wild-types, suggesting that absence of a receptor was able to down-regulate ligand expression [15].
  • Membrane guanylate cyclase C (GC-C) is the receptor for guanylin, uroguanylin, and heat-stable enterotoxin (STa) in the intestine [3].
  • GCAP-II: isolation and characterization of the circulating form of human uroguanylin [16].
  • The upstream promoter sequence of the mouse uroguanylin gene contains a canonical TATA element at the site of transcription initiation and consensus binding sites for several known transcription factors, including HNF-1 and Sp1 within the first 1 kb [17].
  • The intestinal peptide hormone uroguanylin regulates electrolyte/fluid transport in the gastrointestinal epithelium by binding to its receptor, guanylate cyclase C (GC-C), and thus specifically coupling to activation of cystic fibrosis transmembrane conductance regulator (CFTR) [18].

Analytical, diagnostic and therapeutic context of Uroguanylin




  1. Increases in guanylin and uroguanylin in a mouse model of osmotic diarrhea are guanylate cyclase C-independent. Steinbrecher, K.A., Mann, E.A., Giannella, R.A., Cohen, M.B. Gastroenterology (2001) [Pubmed]
  2. Uroguanylin treatment suppresses polyp formation in the Apc(Min/+) mouse and induces apoptosis in human colon adenocarcinoma cells via cyclic GMP. Shailubhai, K., Yu, H.H., Karunanandaa, K., Wang, J.Y., Eber, S.L., Wang, Y., Joo, N.S., Kim, H.D., Miedema, B.W., Abbas, S.Z., Boddupalli, S.S., Currie, M.G., Forte, L.R. Cancer Res. (2000) [Pubmed]
  3. Guanylin, uroguanylin, and heat-stable euterotoxin activate guanylate cyclase C and/or a pertussis toxin-sensitive G protein in human proximal tubule cells. Sindiće, A., Başoglu, C., Cerçi, A., Hirsch, J.R., Potthast, R., Kuhn, M., Ghanekar, Y., Visweswariah, S.S., Schlatter, E. J. Biol. Chem. (2002) [Pubmed]
  4. The molecular basis of hypertension. Garbers, D.L., Dubois, S.K. Annu. Rev. Biochem. (1999) [Pubmed]
  5. Uroguanylin knockout mice have increased blood pressure and impaired natriuretic response to enteral NaCl load. Lorenz, J.N., Nieman, M., Sabo, J., Sanford, L.P., Hawkins, J.A., Elitsur, N., Gawenis, L.R., Clarke, L.L., Cohen, M.B. J. Clin. Invest. (2003) [Pubmed]
  6. Guanylyl cyclase C agonists regulate progression through the cell cycle of human colon carcinoma cells. Pitari, G.M., Di Guglielmo, M.D., Park, J., Schulz, S., Waldman, S.A. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  7. Regulation of intestinal uroguanylin/guanylin receptor-mediated responses by mucosal acidity. Hamra, F.K., Eber, S.L., Chin, D.T., Currie, M.G., Forte, L.R. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  8. Uroguanylin is expressed by enterochromaffin cells in the rat gastrointestinal tract. Perkins, A., Goy, M.F., Li, Z. Gastroenterology (1997) [Pubmed]
  9. Uroguanylin, an intestinal natriuretic peptide, is delivered to the kidney as an unprocessed propeptide. Moss, N.G., Fellner, R.C., Qian, X., Yu, S.J., Li, Z., Nakazato, M., Goy, M.F. Endocrinology. (2008) [Pubmed]
  10. Differential display of intestinal mRNAs regulated by dietary zinc. Blanchard, R.K., Cousins, R.J. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  11. Uroguanylin: structure and activity of a second endogenous peptide that stimulates intestinal guanylate cyclase. Hamra, F.K., Forte, L.R., Eber, S.L., Pidhorodeckyj, N.V., Krause, W.J., Freeman, R.H., Chin, D.T., Tompkins, J.A., Fok, K.F., Smith, C.E. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  12. Lymphoguanylin: cloning and characterization of a unique member of the guanylin peptide family. Forte, L.R., Eber, S.L., Fan, X., London, R.M., Wang, Y., Rowland, L.M., Chin, D.T., Freeman, R.H., Krause, W.J. Endocrinology (1999) [Pubmed]
  13. Enterochromaffin-like cells, a cellular source of uroguanylin in rat stomach. Date, Y., Nakazato, M., Yamaguchi, H., Kangawa, K., Kinoshita, Y., Chiba, T., Ueta, Y., Yamashita, H., Matsukura, S. Endocrinology (1999) [Pubmed]
  14. Salt and water homeostasis: uroguanylin is a circulating peptide hormone with natriuretic activity. Forte, L.R., Fan, X., Hamra, F.K. Am. J. Kidney Dis. (1996) [Pubmed]
  15. High salt intake increases uroguanylin expression in mouse kidney. Potthast, R., Ehler, E., Scheving, L.A., Sindic, A., Schlatter, E., Kuhn, M. Endocrinology (2001) [Pubmed]
  16. GCAP-II: isolation and characterization of the circulating form of human uroguanylin. Hess, R., Kuhn, M., Schulz-Knappe, P., Raida, M., Fuchs, M., Klodt, J., Adermann, K., Kaever, V., Cetin, Y., Forssmann, W.G. FEBS Lett. (1995) [Pubmed]
  17. The uroguanylin gene (Guca1b) is linked to guanylin (Guca2) on mouse chromosome 4. Whitaker, T.L., Steinbrecher, K.A., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Cohen, M.B. Genomics (1997) [Pubmed]
  18. Uroguanylin and guanylate cyclase C in the human pancreas: expression and mutuality of ligand/receptor localization as indicators of intercellular paracrine signaling pathways. Kulaksiz, H., Cetin, Y. J. Endocrinol. (2001) [Pubmed]
  19. Modulation of intestinal gene expression by dietary zinc status: effectiveness of cDNA arrays for expression profiling of a single nutrient deficiency. Blanchard, R.K., Moore, J.B., Green, C.L., Cousins, R.J. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  20. Uroguanylin and guanylin peptides: pharmacology and experimental therapeutics. Forte, L.R. Pharmacol. Ther. (2004) [Pubmed]
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