Urocontrin, a novel UT receptor ligand with a unique pharmacological profile

Biochem Pharmacol. 2012 Mar 1;83(5):608-15. doi: 10.1016/j.bcp.2011.12.009. Epub 2011 Dec 16.

Abstract

In recent years, several studies have demonstrated that urotensin II (UII) and urotensin II-related peptide (URP) can exhibit differential biological activity. So far, known antagonists of the urotensin II receptor (UT) are of limited usefulness for investigating the specific pathophysiological role of UII or URP. Therefore, identification of new compounds able to discriminate UII- and URP-associated biological activities is crucially needed. In the present study, we report preliminary data regarding the pharmacological properties of a novel UT ligand termed urocontrin, i.e. [Bip(4)]URP, that is able to reduce the ex vivo efficacy of hUII- but not URP-induced vasoconstriction in rat aortic rings. In vivo studies support the pharmacological profile described above. Although urocontrin exert some residual agonist activity, this compound should be useful for the rational design of potent molecules that would allow discriminating specific biological action mediated by UII or URP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antihypertensive Agents / pharmacology*
  • Aorta / drug effects
  • CHO Cells
  • Cricetinae
  • Endothelin-1 / pharmacology
  • Hypotension / chemically induced
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Molecular Structure
  • Peptide Hormones / pharmacology*
  • Protein Binding
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, G-Protein-Coupled / metabolism*
  • Urotensins / pharmacology
  • Vasoconstriction / drug effects

Substances

  • Antihypertensive Agents
  • Endothelin-1
  • Intracellular Signaling Peptides and Proteins
  • Peptide Hormones
  • Receptors, G-Protein-Coupled
  • UTS2B protein, human
  • Urotensins
  • Uts2r protein, rat
  • urotensin II-related peptide, 2-amino-3-(1,1'-bipheny-4-yl)propanoic acid(4)-
  • urotensin II