The urotensin-II (U-II) receptor (UT, nomenclature as agreed by the NC-IUPHAR Subcommittee on the Urotensin receptor [12,14,37]) 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 [3,36]. Several structural forms of U-II exist in fish and amphibians [37]. The goby orthologue was used to identify U-II as the cognate ligand for the predicted receptor encoded by the rat gene gpr14 [1,8,22,25,27]. Human urotensin-II (UTS2, O95399), an 11-amino-acid peptide [8], retains the cyclohexapeptide sequence of goby U-II that is thought to be important in ligand binding [4,16,21]. 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 [7]. 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 [13]. UT exhibits relatively high sequence identity with somatostatin, opioid and galanin receptors [37]. The urotensinergic system displays an unprecedented repertoire of four or five ancient UT in some vertebrate lineages and five U-II family peptides in teleost fish [35].

In the human vasculature, human urotensin-II (UTS2, O95399) elicits both vasoconstrictor (pD₂ 9.3-10.1, [23]) and vasodilator (pIC₅₀ 10.3-10.4, [31]) responses.

* 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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Subcommittee members: Hubert Vaudry (Chairperson) Inserm U982 Institute for Research and Innovation in Biomedicine (IRIB) Laboratory of Neuronal and Neuroendocrine Differentiation and Communication Team Neurotrophic Factors and Neuronal Differentiation Associated International Laboratory Samuel de Champlain Regional Platform for Cell Imaging of Haute-Normandie (PRIMACEN) Normandy University F-76000 Rouen, France Alain Fournier INRS-Institut Armand-Frappier Université du Québec 531 boulevard des Prairies Ville de Laval Québec H7V 1B7 Canada Adel Giaid Division of Cardiology Montreal General Hospital McGill University Health Center Montreal Quebec Canada Henry Krum Centre of Cardiovascular Research and Education in Therapeutics Department of Epidemiology & Preventive Medicine Monash University Alfred Hospital Victoria Australia David G. Lambert University Department of Cardiovascular Sciences (Pharmacology and Therapeutics Group) Division of Anaesthesia Critical Care and Pain Management University of Leicester Leicester Royal Infirmary Leicester LE1 5WW UK Jérôme Leprince Inserm U982 Institute for Research and Innovation in Biomedicine (IRIB) Laboratory of Neuronal and Neuroendocrine Differentiation and Communication Team Neurotrophic Factors and Neuronal Differentiation Associated International Laboratory Samuel de Champlain Regional Platform for Cell Imaging of Haute-Normandie (PRIMACEN) Normandy University F-76000 Rouen, France Eliot H. Ohlstein Chief Scientific Officer Velicept Therapeutics 101 Lindenwood Dr Malvern PA 19355 USA Adjunct Professor in Pharmacology Drexel University College of Medicine Hervé Tostivint UMR 7221 CNRS/MNHN Evolution des Régulations Endocriniennes Muséum National d’Histoire Naturelle 75231 Paris France David Vaudry INSERM Unit 982 Institute for Research and Innovation in Biomedicine (IRIB) Laboratory of Neuronal and Neuroendocrine Differentiation and Communication Team Neurotrophic Factors and Neuronal Differentiation Associated International Laboratory Samuel de Champlain Regional Platform for Cell Imaging of Haute-Normandy (PRIMACEN) Normandy University F-76821 Mont-Saint-Aignan, France

Other contributors: Anthony P. Davenport Experimental Medicine and Immunotherapeutics University of Cambridge Addenbrooke’s Hospital Cambridge UK Stephen A. Douglas (Past chairperson) Discovery Translational Medicine S-2321 Wyeth Research 500 Arcola Road Collegeville PA 19426 USA Margaret R. MacLean Professor of Pulmonary Pharmacology Room 417 West Medical Building IBLS Glasgow University Glasgow G12 8QQ Scotland Walter G. Thomas School of Biomedical Sciences The University of Queensland BNE, QUEENSLAND 4072 Australia David J. Webb Centre for Cardiovascular Science Department of Medical Sciences The University of Edinburgh The Queen's Medical Research Institute 3rd Floor East, Room E3.22 47 Little France Crescent Edinburgh EH16 4TJ UK