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Gene Review

Uts2  -  urotensin 2

Mus musculus

Synonyms: U-II, UII, Ucn2, Urotensin II, Urotensin-2, ...
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Disease relevance of Uts2

  • Recently the intense staining of U-II-like immunoreactivity within coronary atheroma and the effect of mitogenic in vascular smooth muscle cells (VSMCs) suggest that U-II is possibly a proatherogenic factor in the pathogenesis of cardiovascular diseases (CVD) [1].

High impact information on Uts2

  • These data are consistent with the hypothesis that Ucn 2 functions as a local negative regulator of glucose uptake in skeletal muscle and encourage exploration of the possibility that suppression of the Ucn 2/CRFR2 pathway may provide benefits in insulin-resistant states such as type 2 diabetes [2].
  • In keeping with these data, Ucn 2 inhibited insulin-induced Akt and ERK1/2 phosphorylation in cultured skeletal muscle cells and C2C12 myotubes [2].
  • We propose that null mutant mice display increased glucose uptake in skeletal muscle through the removal of Ucn 2-mediated inhibition of insulin signaling [2].
  • Using glucose-tolerance tests (GTTs), insulin-tolerance tests (ITTs), and hyperinsulinemic euglycemic glucose clamp studies, we demonstrated that mice lacking Ucn 2 exhibited increased insulin sensitivity and were protected against fat-induced insulin resistance [2].
  • Body composition measurements of Ucn 2-null mice on a high-fat diet demonstrated decreases in fat and increases in lean tissue compared with WT mice [2].

Biological context of Uts2

  • These results suggest that in the ventral horn of the mouse spinal cord both UII and URP precursor and AR mRNA are expressed by the same neurons and that circulating androgens are exerting a down-regulation of the three protein mRNA expression, possibly by a direct action on motoneurons [3].
  • It is postulated that this protein is solely responsible for mediating U-II-induced vasoconstriction [4].
  • Intracerebroventricular injection of U-II also caused an increase in: food intake at doses of 100 and 1,000 ng/mouse, water intake at doses of 100-10,000 ng/mouse, and horizontal locomotion activity at a dose of 10,000 ng/mouse [5].
  • Whatever was the dose, the central administration of U-II had no effect on body temperature, nociception, apomorphine-induced penile erection and climbing behavior, and stress-induced plasma corticosterone level [5].
  • These results indicate that the up-regulation of vascular U-II receptor (UT), GPR14 might be involved in the pathogenesis of atherosclerosis [1].

Anatomical context of Uts2

  • Urotensin-II expression in the mouse spinal cord [6].
  • The addition of urotensin II induced contraction of the ileum in concentration-manner (-log EC(50) value was 8.13+/-0.21) [7].
  • Urotensin-II (U-II) receptors are widely distributed in the central nervous system [5].
  • Urotensin II and its receptor are expressed in the gastrointestinal tract of mice, but the effects of urotensin II on the gastrointestinal functions have not been established [7].
  • Mouse Ucn 2 had no effect on c-Fos expression within the median raphe nucleus, consistent with the hypothesis that Ucn 2 has specific actions on an anatomically and functionally distinct subset of serotonergic neurons via activation of CRF2 receptors [8].

Associations of Uts2 with chemical compounds

  • Administration of synthetic Ucn 2 to mutant mice before the GTTs and ITTs restored blood glucose to WT levels [2].
  • Tetradecapeptide somatostatin (10-80 microM) and its analog urotensin II (0.1-5 microM), a dodecapeptide from the urophysis of the teleost fish Gillichthys mirabilis, produced similar slowly developing relaxations of carbachol-induced tone [9].
  • Treatment with omega-conotoxin GVIA (an inhibitor of N-type Ca(2+) channels, 300 nM) inhibited 100 nM urotensin II- and 4 microM nicotine-, but not 3 microM acetylcholine-, induced contraction [7].
  • Contraction of isolated guinea-pig ileum by urotensin II via activation of ganglionic cholinergic neurons and acetylcholine release [7].
  • Like nicotine, the contraction induced by 100 nM urotensin II was inhibited by treatment with atropine, hexamethonium, D-tubocurarine, tetrodotoxin or hemicholinium-3, and enhanced by physostigmine [7].

Regulatory relationships of Uts2


Other interactions of Uts2


Analytical, diagnostic and therapeutic context of Uts2


  1. Alteration of vascular urotensin II receptor in mice with apolipoprotein E gene knockout. Wang, Z.J., Shi, L.B., Xiong, Z.W., Zhang, L.F., Meng, L., Bu, D.F., Tang, C.S., Ding, W.H. Peptides (2006) [Pubmed]
  2. Urocortin 2 modulates glucose utilization and insulin sensitivity in skeletal muscle. Chen, A., Brar, B., Choi, C.S., Rousso, D., Vaughan, J., Kuperman, Y., Kim, S.N., Donaldson, C., Smith, S.M., Jamieson, P., Li, C., Nagy, T.R., Shulman, G.I., Lee, K.F., Vale, W. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  3. Androgenic down-regulation of urotensin II precursor, urotensin II-related peptide precursor and androgen receptor mRNA in the mouse spinal cord. Pelletier, G., Lihrmann, I., Dubessy, C., Luu-The, V., Vaudry, H., Labrie, F. Neuroscience (2005) [Pubmed]
  4. Deletion of the UT receptor gene results in the selective loss of urotensin-II contractile activity in aortae isolated from UT receptor knockout mice. Behm, D.J., Harrison, S.M., Ao, Z., Maniscalco, K., Pickering, S.J., Grau, E.V., Woods, T.N., Coatney, R.W., Doe, C.P., Willette, R.N., Johns, D.G., Douglas, S.A. Br. J. Pharmacol. (2003) [Pubmed]
  5. Behavioral effects of urotensin-II centrally administered in mice. Do-Rego, J.C., Chatenet, D., Orta, M.H., Naudin, B., Le Cudennec, C., Leprince, J., Scalbert, E., Vaudry, H., Costentin, J. Psychopharmacology (Berl.) (2005) [Pubmed]
  6. Urotensin-II expression in the mouse spinal cord. Egginger, J.G., Camus, A., Calas, A. J. Chem. Neuroanat. (2006) [Pubmed]
  7. Contraction of isolated guinea-pig ileum by urotensin II via activation of ganglionic cholinergic neurons and acetylcholine release. Horie, S., Yasuda, S., Tsurumaki, Y., Someya, A., Saito, T., Okuma, Y., Nomura, Y., Hirabayashi, T., Murayama, T. Neuropharmacology (2003) [Pubmed]
  8. Evidence supporting a role for corticotropin-releasing factor type 2 (CRF2) receptors in the regulation of subpopulations of serotonergic neurons. Staub, D.R., Evans, A.K., Lowry, C.A. Brain Res. (2006) [Pubmed]
  9. Neuropeptide-induced contraction and relaxation of the mouse anococcygeus muscle. Gibson, A., Bern, H.A., Ginsburg, M., Botting, J.H. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  10. Urotensin II stimulates plasma extravasation in mice via UT receptor activation. Vergura, R., Camarda, V., Rizzi, A., Spagnol, M., Guerrini, R., Calo', G., Salvadori, S., Regoli, D. Naunyn Schmiedebergs Arch. Pharmacol. (2004) [Pubmed]
  11. Urotensin II and cardiovascular diseases. Thanassoulis, G., Huyhn, T., Giaid, A. Peptides (2004) [Pubmed]
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