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Gene Review

Uts2  -  urotensin 2

Rattus norvegicus

Synonyms: U-II, UII, Urotensin II, Urotensin-2
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Disease relevance of Uts2


Psychiatry related information on Uts2


High impact information on Uts2


Chemical compound and disease context of Uts2

  • U-II was equally as efficacious as phenylephrine in inducing hypertrophy, measured by a reporter assay (EC(50) 0.7+/-0.2 nM) and [(3)H]-leucine incorporation (EC(50) 150+/-40 nM) [3].
  • U-II shares similar biological activities with other hypertrophic G(q)-coupled receptor ligands such as angiotensin-II and endothelin-1, but a role for U-II in cardiomyocyte hypertrophy has not been characterized [3].
  • Results: The ratio of heart weight/body weight, plasma lactate dehydrogenase activity, myocardial malondialdehyde and hydroxyproline concentration increased significantly in the ISO group, as well as UT mRNA expression, plasma and cardiac UII and ventricular Ang II, compared with the control group (P< 0.01) [8].
  • Urotensin II accelerates cardiac fibrosis and hypertrophy of rats induced by isoproterenol [8].
  • In vitro, 5 X10(-9 )-5 X10(-7 ) mol/L UII stimulated [3H]thymidine/[3H] proline incorporation into cardiac fibroblasts in a dose-dependent manner (P< 0.01).Conclusion: These results suggest that UII was involved in the development of cardiac fibrosis and hypertrophy by synergistic effects with ISO [8].

Biological context of Uts2

  • Cloning, sequence analysis and tissue distribution of the mouse and rat urotensin II precursors [9].
  • These results indicate that UII produces vasodilator and natriuretic effects in the kidney and that UII-induced vasodilation is associated with increased endothelial NO in the RA [10].
  • In the present study, we have investigated the localization of UII receptor (GPR14) mRNA and UII binding sites in the rat CNS [11].
  • Thus, UII is the first gene reported to show expression limited to the sacral pool of motoneurons, which are known to have particular properties in terms of targets and programmed cell death [12].
  • These results indicate that circulating androgens are exerting a down-regulation of pro UII expression possibly by a direct action at the level of motoneurons [13].

Anatomical context of Uts2


Associations of Uts2 with chemical compounds

  • This distribution suggests that the UII system is involved in functions regulated by acetylcholine, such as the sleep-wake cycle [6].
  • Pre-treatment with pentolinium (5 mg/kg, i.v.) significantly attenuated the increases in mean arterial pressure (20 +/- 3 versus 8 +/- 2 mmHg, P <0.01) and heart rate (78 +/- 18 versus 7 +/- 5 beats/min, P <0.05) induced by ICV urotensin II [15].
  • Human U-II was a potent vasoconstrictor of endothelium-intact isolated rat thoracic aorta (EC(50)=3.5+/-1.1 nM, R(max)=103+/-10% of control contraction induced by 60 mM KCl and 1 microM noradrenaline) [16].
  • Moreover, human U-II caused concentration-dependent relaxation of 5-HT-precontracted arteries, which was abolished by L-NAME or removal of the endothelium [16].
  • Human U-II contracted endothelium-intact rat isolated left anterior descending coronary arteries (EC(50)=1.3+/-0.8 nM, R(max)=20.1+/-4.9% of control contraction induced by 10 microM 5-HT) [16].

Regulatory relationships of Uts2


Other interactions of Uts2


Analytical, diagnostic and therapeutic context of Uts2

  • The present study suggests an important role for UII in the pathogenesis of restenosis following balloon angioplasty [14].
  • Moreover, whole-cell recordings from rat-brain slices show that UII selectively excites cholinergic PPT neurons via an inward current and membrane depolarization that were accompanied by membrane conductance decreases [6].
  • UII mRNA was detected by reverse-transcription-polymerase chain reaction (RT-PCR) as early as E10 [12].
  • Three weeks after castration, pro UII mRNA expression, as measured by semi-quantitative in situ hybridization, was increased by 17% and 58% in the ventral horn of the spinal cord and the facial nucleus, respectively [13].
  • Pancreatic extracts were analyzed for UII by reversed-phase HPLC combined with a sensitive UII RIA [21].


  1. Urotensin II promotes hypertrophy of cardiac myocytes via mitogen-activated protein kinases. Onan, D., Pipolo, L., Yang, E., Hannan, R.D., Thomas, W.G. Mol. Endocrinol. (2004) [Pubmed]
  2. Urotensin II induces hypertrophic responses in cultured cardiomyocytes from neonatal rats. Zou, Y., Nagai, R., Yamazaki, T. FEBS Lett. (2001) [Pubmed]
  3. Urotensin-II-mediated cardiomyocyte hypertrophy: effect of receptor antagonism and role of inflammatory mediators. Johns, D.G., Ao, Z., Naselsky, D., Herold, C.L., Maniscalco, K., Sarov-Blat, L., Steplewski, K., Aiyar, N., Douglas, S.A. Naunyn Schmiedebergs Arch. Pharmacol. (2004) [Pubmed]
  4. Central cardiovascular action of urotensin II in spontaneously hypertensive rats. Lin, Y., Tsuchihashi, T., Matsumura, K., Fukuhara, M., Ohya, Y., Fujii, K., Iida, M. Hypertens. Res. (2003) [Pubmed]
  5. The upregulation of endothelial nitric oxide synthase and urotensin-II is associated with pulmonary hypertension and vascular diseases in rats produced by aortocaval shunting. Qi, J., Du, J., Tang, X., Li, J., Wei, B., Tang, C. Heart and vessels. (2004) [Pubmed]
  6. Urotensin II modulates rapid eye movement sleep through activation of brainstem cholinergic neurons. Huitron-Resendiz, S., Kristensen, M.P., Sánchez-Alavez, M., Clark, S.D., Grupke, S.L., Tyler, C., Suzuki, C., Nothacker, H.P., Civelli, O., Criado, J.R., Henriksen, S.J., Leonard, C.S., de Lecea, L. J. Neurosci. (2005) [Pubmed]
  7. Role of ERK and Rho kinase pathways in central pressor action of urotensin II. Lin, Y., Matsumura, K., Tsuchihashi, T., Fukuhara, M., Fujii, K., Iida, M. J. Hypertens. (2004) [Pubmed]
  8. Urotensin II accelerates cardiac fibrosis and hypertrophy of rats induced by isoproterenol. Zhang, Y.G., Li, Y.G., Liu, B.G., Wei, R.H., Wang, D.M., Tan, X.R., Bu, D.F., Pang, Y.Z., Tang, C.S. Acta Pharmacol. Sin. (2007) [Pubmed]
  9. Cloning, sequence analysis and tissue distribution of the mouse and rat urotensin II precursors. Coulouarn, Y., Jégou, S., Tostivint, H., Vaudry, H., Lihrmann, I. FEBS Lett. (1999) [Pubmed]
  10. Urotensin II is a nitric oxide-dependent vasodilator and natriuretic peptide in the rat kidney. Zhang, A.Y., Chen, Y.F., Zhang, D.X., Yi, F.X., Qi, J., Andrade-Gordon, P., de Garavilla, L., Li, P.L., Zou, A.P. Am. J. Physiol. Renal Physiol. (2003) [Pubmed]
  11. Localization of the urotensin II receptor in the rat central nervous system. Jégou, S., Cartier, D., Dubessy, C., Gonzalez, B.J., Chatenet, D., Tostivint, H., Scalbert, E., LePrince, J., Vaudry, H., Lihrmann, I. J. Comp. Neurol. (2006) [Pubmed]
  12. Specific expression of the urotensin II gene in sacral motoneurons of developing rat spinal cord. Coulouarn, Y., Fernex, C., Jégou, S., Henderson, C.E., Vaudry, H., Lihrmann, I. Mech. Dev. (2001) [Pubmed]
  13. Role of androgens in the regulation of urotensin II precursor mRNA expression in the rat brainstem and spinal cord. Pelletier, G., Lihrmann, I., Vaudry, H. Neuroscience (2002) [Pubmed]
  14. A role for urotensin II in restenosis following balloon angioplasty: use of a selective UT receptor blocker. Rakowski, E., Hassan, G.S., Dhanak, D., Ohlstein, E.H., Douglas, S.A., Giaid, A. J. Mol. Cell. Cardiol. (2005) [Pubmed]
  15. Central cardiovascular action of urotensin II in conscious rats. Lin, Y., Tsuchihashi, T., Matsumura, K., Abe, I., Iida, M. J. Hypertens. (2003) [Pubmed]
  16. Human urotensin-II is an endothelium-dependent vasodilator in rat small arteries. Bottrill, F.E., Douglas, S.A., Hiley, C.R., White, R. Br. J. Pharmacol. (2000) [Pubmed]
  17. Specificity of response of intestinal ion transport systems to a pair of natural peptide hormone analogs: somatostatin and urotensin II. Loretz, C.A., Freel, R.W., Bern, H.A. Gen. Comp. Endocrinol. (1983) [Pubmed]
  18. Urotensin II-induced activation of extracellular signal-regulated kinase in cultured vascular smooth muscle cells: involvement of cell adhesion-mediated integrin signaling. Tamura, K., Okazaki, M., Tamura, M., Isozumi, K., Tasaki, H., Nakashima, Y. Life Sci. (2003) [Pubmed]
  19. Urotensin-II, a neuropeptide ligand for GPR14, induces c-fos in the rat brain. Gartlon, J.E., Ashmeade, T., Duxon, M., Hagan, J.J., Jones, D.N. Eur. J. Pharmacol. (2004) [Pubmed]
  20. Role of prostaglandins in urotensin II-induced vasodilatation in the coronary arteries of aged rats. Ishihata, A., Ogaki, T., Aita, T., Katano, Y. Eur. J. Pharmacol. (2005) [Pubmed]
  21. Urotensin-II is present in pancreatic extracts and inhibits insulin release in the perfused rat pancreas. Silvestre, R.A., Egido, E.M., Hernández, R., Leprince, J., Chatenet, D., Tollemer, H., Chartrel, N., Vaudry, H., Marco, J. Eur. J. Endocrinol. (2004) [Pubmed]
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