Urotensin receptor

Overview

The urotensin-II (U-II) receptor (UT) is activated by the endogenous dodecapeptide urotensin-II, originally isolated from the urophysis, the endocrine organ of the caudal neurosecretory system of teleost fish [1,2]. Several... [read more] structural forms of U-II exist in fish and amphibians [3]. The goby orthologue was used to identify U-II as the cognate ligand for the predicted receptor encoded by the rat gene gpr14 [4,5,6,7,8]. Human urotensin-II, an 11-amino-acid peptide [5], retains the cyclohexapeptide sequence of goby U-II that is thought to be important in ligand binding [9,10,11]. 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 [12]. A second endogenous ligand for the UT has been discovered in rat [13]. This is the urotensin II-related peptide, 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 are predicted for the mature mouse and human peptides [14]. UT exhibits relatively high sequence identity with somatostatin, opioid and galanin receptors [3].

References

1. Bern HA, Pearson D, Larson BA, et al. Neurohormones from fish tails: the caudal neurosecretory system. I: "Urophysiology" and the caudal neurosecretory system of fishes. Recent Prog Horm Res 1985;41:533-552.
2. Vaudry H, Do Rego JC, Le Mevel JC, et al. Urotensin II, from fish to human. Ann N Y Acad Sci 2010;1200:53-66.
3. Vaudry H, Leprince J, Chatenet D, et al. International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, urotensin II-related peptide, and their receptor: from structure to function. Pharmacol Rev 2015;67:214-58.
4. Ames RS, Sarau HM, Chambers JK, et al. Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14. Nature 1999;401:282-6.
5. Coulouarn Y, Lihrmann I, Jegou S, et al. 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 USA 1998;95:15803-8.
6. Liu Q, Pong SS, Zeng Z, et al. Identification of urotensin II as the endogenous ligand for the orphan G-protein-coupled receptor GPR14. Biochem Biophys Res Commun 1999;266:174-8.
7. Mori M, Sugo T, Abe M, et al. Urotensin II is the endogenous ligand of a G-protein-coupled orphan receptor, SENR (GPR14). Biochem Biophys Res Commun 1999;265:123-9.
8. Nothacker HP, Wang Z, McNeill AM, et al. Identification of the natural ligand of an orphan G-protein-coupled receptor involved in the regulation of vasoconstriction. Nat Cell Biol 1999;1:383-5.
9. Leprince J, Chatenet D, Dubessy C, et al. Structure-activity relationships of urotensin II and URP. Peptides 2008;29:658-73.
10. Kinney WA, Almond Jr HR, Qi J, et al. Structure-function analysis of urotensin II and its use in the construction of a ligand-receptor working model. Angew Chem Int Ed Engl 2002;41:2940-4.
11. Brkovic A, Hattenberger A, Kostenis E, et al. Functional and binding characterizations of urotensin II-related peptides in human and rat urotensin II-receptor assay. J Pharmacol Exp Ther 2003;306:1200-9.
12. Coulouarn Y, Jégou S, Tostivint H, et al. Cloning, sequence analysis and tissue distribution of the mouse and rat urotensin II precursors. FEBS Lett 1999;457:28-32.
13. Sugo T, Mori M. Another ligand fishing for G protein-coupled receptor 14. Discovery of urotensin II-related peptide in the rat brain. Peptides 2008;29:809-12.
14. Dubessy C, Cartier D, Lectez B, et al. 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 2008;107:361-74.

[close]