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Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
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The urotensin-II (U-II) receptor (UT, nomenclature as agreed by the NC-IUPHAR Subcommittee on the Urotensin receptor [13,17,35]) is activated by the endogenous dodecapeptide urotensin-II (UTS2, O95399), originally isolated from the urophysis, the endocrine organ of the caudal neurosecretory system of teleost fish [3,34]. 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 [9,24,27-28]. Human urotensin-II (UTS2, O95399), an 11-amino-acid peptide [9], retains the cyclohexapeptide sequence of goby U-II that is thought to be important in ligand binding [5,19]. This sequence is also conserved in the deduced amino-acid sequence of rat urotensin-II (14 amino-acids) and mouse urotensin-II (14 amino-acids), although the N-terminal is more divergent from the human sequence [8]. A second endogenous ligand for the UT has been discovered in rat [32]. This is the urotensin II-related peptide (UTS2B, Q765I0), an octapeptide that is derived from a different gene, but shares the C-terminal sequence (CFWKYCV) common to U-II from other species. Identical sequences to rat urotensin II-related peptide (UTS2B, Q765I0) are predicted for the mature mouse and human peptides [15]. UT exhibits relatively high sequence identity with somatostatin, opioid and galanin receptors [35].
UT receptor
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* Key recommended reading is highlighted with an asterisk
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 SM, Bonner TI, Neubig RR, Rosser EM, Pin JP, Davenport AP, Spedding M, Harmar AJ. (2005) International Union of Pharmacology. XLVI. G protein-coupled receptor list. Pharmacol. Rev., 57 (2): 279-88. [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, Leprince J, Chatenet D, Fournier A, Lambert DG, Le Mével JC, Ohlstein EH, Schwertani A, Tostivint H, Vaudry D. (2015) International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, urotensin II-related peptide, and their receptor: from structure to function. Pharmacol. Rev., 67 (1): 214-58. [PMID:25535277]
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9. Coulouarn Y, Lihrmann I, Jegou S, Anouar Y, Tostivint H, Beauvillain JC, Conlon JM, Bern HA, 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 (26): 15803-8. [PMID:9861051]
10. Croston GE, Olsson R, Currier EA, Burstein ES, Weiner D, Nash N, Severance D, Allenmark SG, Thunberg L, Ma JN et al.. (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 (23): 4950-3. [PMID:12408704]
11. Diallo M, Jarry M, Desrues L, Castel H, Chatenet D, Leprince J, Vaudry H, Tonon MC, Gandolfo P. (2008) [Orn5]URP acts as a pure antagonist of urotensinergic receptors in rat cortical astrocytes. Peptides, 29 (5): 813-9. [PMID:18082287]
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14. Douglas SA, Behm DJ, Aiyar NV, Naselsky D, Disa J, Brooks DP, Ohlstein EH, Gleason JG, Sarau HM, Foley JJ et al.. (2005) Nonpeptidic urotensin-II receptor antagonists I: in vitro pharmacological characterization of SB-706375. Br. J. Pharmacol., 145 (5): 620-35. [PMID:15852036]
15. Dubessy C, Cartier D, Lectez B, Bucharles C, Chartrel N, Montero-Hadjadje M, Bizet P, Chatenet D, Tostivint H, Scalbert E et al.. (2008) Characterization of urotensin II, distribution of urotensin II, urotensin II-related peptide and UT receptor mRNAs in mouse: evidence of urotensin II at the neuromuscular junction. J. Neurochem., 107 (2): 361-74. [PMID:18710417]
16. Elshourbagy NA, Douglas SA, Shabon U, Harrison S, Duddy G, Sechler JL, Ao Z, Maleeff BE, Naselsky D, Disa J et al.. (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 (1): 9-22. [PMID:11976263]
17. Foord SM, Bonner TI, Neubig RR, Rosser EM, Pin JP, Davenport AP, Spedding M, Harmar AJ. (2005) International Union of Pharmacology. XLVI. G protein-coupled receptor list. Pharmacol. Rev., 57 (2): 279-88. [PMID:15914470]
18. Grieco P, Carotenuto A, Campiglia P, Zampelli E, Patacchini R, Maggi CA, Novellino E, Rovero P. (2002) A new, potent urotensin II receptor peptide agonist containing a Pen residue at the disulfide bridge. J. Med. Chem., 45 (20): 4391-4. [PMID:12238917]
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34. 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]
35. Vaudry H, Leprince J, Chatenet D, Fournier A, Lambert DG, Le Mével JC, Ohlstein EH, Schwertani A, Tostivint H, Vaudry D. (2015) International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, urotensin II-related peptide, and their receptor: from structure to function. Pharmacol. Rev., 67 (1): 214-58. [PMID:25535277]
Subcommittee members:
Hubert Vaudry (Chairperson)
Alain Fournier
Adel Giaid
Henry Krum
David G. Lambert
Jérôme Leprince
Eliot H. Ohlstein
Hervé Tostivint
David Vaudry |
Other contributors:
Anthony P. Davenport
Stephen A. Douglas (Past chairperson)
Margaret R. MacLean
Walter G. Thomas
David J. Webb |
Database page citation (select format):
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Christopoulos A, Davenport AP, Kelly E, Mathie A, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Pawson AJ, Sharman JL, Southan C, Davies JA; CGTP Collaborators. (2019) The Concise Guide to PHARMACOLOGY 2019/20: G protein-coupled receptors. Br J Pharmacol. 176 Issue S1: S21-S141.
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In the human vasculature, human urotensin-II (UTS2, O95399) elicits both vasoconstrictor (pD2 9.3-10.1, [25]) and vasodilator (pIC50 10.3-10.4, [31]) responses.