More information on this family may be found on the IUPHAR-DB family and introduction pages.
The urotensin-II (U-II) receptor (UT, nomenclature as agreed by NC-IUPHAR, [8,11]) is activated by the endogenous dodecapeptide U-II, originally isolated from the urophysis, the endocrine organ of the caudal neurosecretory system of teleost fish [2]. Several structural forms of U-II exist in fish and amphibians. The Goby orthologue was used to identify U-II as the cognate ligand for the predicted receptor encoded by the rat gene gpr14 [6,17,20-21]. Human U-II (derived from ENSG00000049247), an 11-amino-acid peptide [6], retains the cyclohexapeptide sequence of goby U-II that is thought to be important in ligand binding [3,13]. This sequence is also conserved in the deduced amino-acid sequence of rat U-II (14 amino-acids) and mouse U-II (14 amino-acids), although the N-terminal is more divergent from the human sequence [5]. A second endogenous ligand for UT has been discovered in rat [25]. The urotensin II-related peptide (URP), an octapeptide, is derived from a different gene, but shares the C-terminal sequence (CFWKYCV) common to U-II from other species. Identical sequences to rat URP are predicted for the mature mouse and human peptides.
Unless otherwise stated all data refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Receptors 
|
Desai, N; Sajjad, J; Frishman, WH. (2008) Urotensin II: a new pharmacologic target in the treatment of cardiovascular disease. Cardiol Rev, 16 (3): 142-53. [PMID:18414185]
Douglas SA, Ohlstein EH. (2000) Urotensin receptors. in The IUPHAR Receptor Compendium of Receptor Characterization and Classification. Edited by Girdlestone D IUPHAR Media Ltd. 365–372
Foord, S. M., Bonner, T. I., Neubig, R. R., Rosser, E. M., Pin, J. P., Davenport, A. P., Spedding, M. and Harmar, A. J. (2005) International Union of Pharmacology. XLVI. G protein-coupled receptor list. Pharmacol Rev, 57: 279-288. [PMID:15914470]
Guidolin, D; Albertin, G; Ribatti, D. (2010) Urotensin-II as an angiogenic factor. Peptides, 31 (6): 1219-24. [PMID:20346384]
Hunt, BD; Ng, LL; Lambert, DG. (2010) A rat brain atlas of urotensin-II receptor expression and a review of central urotensin-II effects. Naunyn Schmiedebergs Arch. Pharmacol., 382 (1): 1-31. [PMID:20422157]
Leprince, J; Chatenet, D; Dubessy, C; Fournier, A; Pfeiffer, B; Scalbert, E; Renard, P; Pacaud, P; Oulyadi, H; Ségalas-Milazzo, I; et al.. (2008) Structure-activity relationships of urotensin II and URP. Peptides, 29 (5): 658-73. [PMID:17931747]
Maryanoff, BE; Kinney, WA. (2010) Urotensin-II receptor modulators as potential drugs. J. Med. Chem., 53 (7): 2695-708. [PMID:20043680]
Ong, KL; Wong, LY; Cheung, BM. (2008) The role of urotensin II in the metabolic syndrome. Peptides, 29 (5): 859-67. [PMID:17610998]
Proulx, CD; Holleran, BJ; Lavigne, P; Escher, E; Guillemette, G; Leduc, R. (2008) Biological properties and functional determinants of the urotensin II receptor. Peptides, 29 (5): 691-9. [PMID:18155322]
Ross, B; McKendy, K; Giaid, A. (2010) Role of urotensin II in health and disease. Am. J. Physiol. Regul. Integr. Comp. Physiol., 298 (5): R1156-72. [PMID:20421634]
Vaudry, H; Do Rego, JC; Le Mevel, JC; Chatenet, D; Tostivint, H; Fournier, A; Tonon, MC; Pelletier, G; Conlon, JM; Leprince, J. (2010) Urotensin II, from fish to human. Ann. N. Y. Acad. Sci., 1200: 53-66. [PMID:20633133]
1. Ames, R. S., Sarau, H. M., Chambers, J. K., Willette, R. N., Aiyar, N. V., Romanic, A. M., Louden, C. S., Foley, J. J., Sauermelch, C. F., Coatney, R. W., Ao, Z., Disa, J., Holmes, S. D., Stadel, J. M., Martin, J. D., Liu, W. S., Glover, G. I., Wilson, S., McNulty, D. E., Ellis, C. E., Elshourbagy, N. A., Shabon, U., Trill, J. J., Hay, D. W., Douglas, S. A. et al.. (1999) Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14. Nature, 401: 282-286. [PMID:10499587]
2. Bern, H. A., Pearson, D., Larson, B. A. and Nishioka, R. S. (1985) Neurohormones from fish tails: the caudal neurosecretory system. I: "Urophysiology" and the caudal neurosecretory system of fishes. Recent Prog. Horm. Res., 41: 533-552. [PMID:2864726]
3. Brkovic, A., Hattenberger, A., Kostenis, E., Klabunde, T., Flohr, S., Kurz, M., Bourgault, S. and Fournier, A. (2003) Functional and binding characterizations of urotensin II-related peptides in human and rat urotensin II-receptor assay. J. Pharmacol. Expl Ther., 306: 1200-1209. [PMID:12807997]
4. Clozel, M; Binkert, C; Birker-Robaczewska, M; Boukhadra, C; Ding, SS; Fischli, W; Hess, P; Mathys, B; Morrison, K; Müller, C; et al.. (2004) Pharmacology of the urotensin-II receptor antagonist palosuran (ACT-058362; 1-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea sulfate salt): first demonstration of a pathophysiological role of the urotensin System. J. Pharmacol. Exp. Ther., 311 (1): 204-12. [PMID:15146030]
5. Coulouarn, Y., Jegou, S., Tostivint, H., Vaudry, H. and Lihrmann, I. (1999) Cloning, sequence analysis and tissue distribution of the mouse and rat urotensin II precursors. FEBS Lett., 457: 28-32. [PMID:10486557]
6. Coulouarn, Y., Lihrmann, I., Jegou, S., Anouar, Y., Tostivint, H., Beauvillain, J. C., Conlon, J. M., Bern, H. A. and Vaudry, H. (1998) Cloning of the cDNA encoding the urotensin II precursor in frog and human reveals intense expression of the urotensin II gene in motoneurons of the spinal cord. Proc. Natl. Acad. Sci. U.S.A., 95: 15803-15808. [PMID:9861051]
7. Croston, G. E., Olsson, R., Currier, E. A., Burstein, E. S., Weiner, D., Nash, N., Severance, D., Allenmark, S. G., Thunberg, L., Ma, J. N., Mohell, N., O'Dowd, B., Brann, M.R. and Hacksell, U. (2002) Discovery of the first nonpeptide agonist of the GPR14/urotensin-II receptor: 3-(4-chlorophenyl)-3-(2- (dimethylamino)ethyl)isochroman-1-one (AC-7954). J. Med. Chem., 45: 4950-4953. [PMID:12408704]
8. Douglas SA, Ohlstein EH. (2000) Urotensin receptors. in The IUPHAR Receptor Compendium of Receptor Characterization and Classification. Edited by Girdlestone D IUPHAR Media Ltd. 365–372
9. Douglas, S. A., Behm, D. J., Aiyar, N. V., Naselsky, D., Disa, J., Brooks, D. P., Ohlstein, E. H., Gleason, J. G., Sarau, H. M., Foley, J. J., Buckley, P. T., Schmidt, D. B., Wixted, W. E., Widdowson, K., Riley, G., Jin, J., Gallagher, T. F., Schmidt, S. J., Ridgers, L., Christmann, L. T., Keenan, R. M., Knight, S. D. and Dhanak, D. (2005) Nonpeptidic urotensin-II receptor antagonists I: in vitro pharmacological characterization of SB-706375. Br J Pharmacol, 145: 620-635. [PMID:15852036]
10. Elshourbagy, N. A., Douglas, S. A., Shabon, U., Harrison, S., Duddy, G., Sechler, J. L., Ao, Z., Maleeff, B. E., Naselsky, D., Disa, J. and Aiyar, N.V. (2002) Molecular and pharmacological characterization of genes encoding urotensin-II peptides and their cognate G-protein-coupled receptors from the mouse and monkey. Br. J. Pharmacol., 136: 9-22. [PMID:11976263]
11. Foord, S. M., Bonner, T. I., Neubig, R. R., Rosser, E. M., Pin, J. P., Davenport, A. P., Spedding, M. and Harmar, A. J. (2005) International Union of Pharmacology. XLVI. G protein-coupled receptor list. Pharmacol Rev, 57: 279-288. [PMID:15914470]
12. Grieco, P., Carotenuto, A., Campiglia, P., Zampelli, E., Patacchini, R., Maggi, C.A., Novellino, E. and Rovero, P. (2002) A new, potent urotensin II receptor peptide agonist containing a Pen residue at the disulfide bridge. J. Med. Chem., 45: 4391-4394. [PMID:12238917]
13. Kinney, W. A., Almond, H. R. Jr., Qi, J., Smith, C. E., Santulli, R. J., de Garavilla, L., Andrade-Gordon, P., Cho, D. S., Everson, A. M., Feinstein, M. A., Leung, P. A. and Maryanoff, B. E. (2002) Structure-function analysis of urotensin II and its use in the construction of a ligand-receptor working model. Angew. Chem. Int. Ed. Engl., 41: 2940-2944. [PMID:12203418]
14. Lehmann, F; Currier, EA; Clemons, B; Hansen, LK; Olsson, R; Hacksell, U; Luthman, K. (2009) Novel and potent small-molecule urotensin II receptor agonists. Bioorg. Med. Chem., 17 (13): 4657-65. [PMID:19481466]
15. Lehmann, F; Currier, EA; Olsson, R; Hacksell, U; Luthman, K. (2005) Isochromanone-based urotensin-II receptor agonists. Bioorg. Med. Chem., 13 (8): 3057-68. [PMID:15781415]
16. Lehmann, F; Lake, L; Currier, EA; Olsson, R; Hacksell, U; Luthman, K. (2007) Design, parallel synthesis and SAR of novel urotensin II receptor agonists. Eur J Med Chem, 42 (2): 276-85. [PMID:17112638]
17. Liu, Q., Pong, S. S., Zeng, Z., Zhang, Q., Howard, A. D., Williams, D. L. Jr., Davidoff, M., Wang, R., Austin, C. P., McDonald, T. P., Bai, C., George, S. R., Evans, J. F. and Caskey, C. T. (1999) Identification of urotensin II as the endogenous ligand for the orphan G-protein-coupled receptor GPR14. Biochem. Biophys. Res. Commun., 266: 174-178. [PMID:10581185]
18. Maguire, J. J., Kuc, R. E. and Davenport, A. P. (2000) Orphan-receptor ligand human urotensin II: receptor localization in human tissues and comparison of vasoconstrictor responses with endothelin-1. Br. J. Pharmacol., 131: 441-446. [PMID:11015293]
19. Marchese, A., Heiber, M., Nguyen, T., Heng, H. H., Saldivia, V. R., Cheng, R., Murphy, P. M., Tsui, L. C., Shi, X., Gregor, P. et al.. (1995) Cloning and chromosomal mapping of three novel genes, GPR9, GPR10, and GPR14, encoding receptors related to interleukin 8, neuropeptide Y, and somatostatin receptors. Genomics, 29: 335-344. [PMID:8666380]
20. Mori, M., Sugo, T., Abe, M., Shimomura, Y., Kurihara, M., Kitada, C., Kikuchi, K., Shintani, Y., Kurokawa, T., Onda, H., Nishimura, O. and Fujino, M. (1999) Urotensin II is the endogenous ligand of a G-protein-coupled orphan receptor, SENR (GPR14). Biochem. Biophys. Res. Commun., 265: 123-129. [PMID:10548501]
21. Nothacker, H.-P., Wang, Z., McNeill, A. M., Saito, Y., Merten, S., O'Dowd, B., Duckles, S. P. and Civelli, O. (1999) Identification of the natural ligand of an orphan G-protein-coupled receptor involved in the regulation of vasoconstriction. Nat. Cell Biol., 1: 383-385. [PMID:10559967]
22. Patacchini, R., Santicioli, P., Giuliani, S., Grieco, P., Novellino, E., Rovero, P. and Maggi, C.A. (2003) Urantide, an ultrapotent urotensin II antagonist peptide in the rat aorta. Br. J. Pharmacol., 140: 1155-1158. [PMID:14645137]
23. Rakowski, E; Hassan, GS; Dhanak, D; Ohlstein, EH; Douglas, SA; Giaid, A. (2005) A role for urotensin II in restenosis following balloon angioplasty: use of a selective UT receptor blocker. J. Mol. Cell. Cardiol., 39 (5): 785-91. [PMID:16171813]
24. Stirrat, A; Gallagher, M; Douglas, SA; Ohlstein, EH; Berry, C; Kirk, A; Richardson, M; MacLean, MR. (2001) Potent vasodilator responses to human urotensin-II in human pulmonary and abdominal resistance arteries. Am. J. Physiol. Heart Circ. Physiol., 280 (2): H925-8. [PMID:11158995]
25. Sugo, T; Mori, M. (2008) Another ligand fishing for G protein-coupled receptor 14. Discovery of urotensin II-related peptide in the rat brain. Peptides, 29 (5): 809-12. [PMID:17628210]
26. Tal, M., Ammar, D. A., Karpuj, M., Krizhanovsky, V., Naim, M. and Thompson, D. A. (1995) A novel putative neuropeptide receptor expressed in neural tissue, including sensory epithelia. Biochem. Biophys. Res. Commun., 209: 752-759. [PMID:7733947]
|
 @GuidetoPHARM  Like us on Facebook Privacy and Cookie Policy |
In human vasculature, human U-II elicits both vasoconstrictor (pD2 9.3–10.1, [18]) and vasodilator (pIC50 10.3–10.4, [24]) responses.