A new ligand for the urotensin II receptor

Br J Pharmacol. 2002 Oct;137(3):311-4. doi: 10.1038/sj.bjp.0704895.


The cyclic peptide human urotensin II (U-II) has been recently recognized as the endogenous ligand of an orphan GPCR, subsequently named the UT receptor. No synthetic ligands are available for investigating this novel peptide-receptor system. A novel UT receptor ligand, [Orn(8)]U-II, was synthesized and evaluated in calcium functional assays performed on HEK293 cells expressing the recombinant rat and human UT receptor and in the rat aorta bioassay. [Orn(8)]U-II behaves as a full agonist (pEC(50) approximately equal 8) at both human and rat UT receptors in the FlipR calcium assay eliciting similar maximal effects as the natural ligand U-II. On the contrary, in the rat aorta bioassay, [Orn(8)]U-II behaves as a competitive and selective antagonist (pA(2)=6.56) showing however a small but consistent residual agonist activity. It is therefore proposed that [Orn(8)]U-II is a partial agonist at UT receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / physiology
  • Calcium / metabolism
  • Cell Line
  • Dose-Response Relationship, Drug
  • Humans
  • In Vitro Techniques
  • Ligands
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cell Surface / agonists*
  • Receptors, Cell Surface / antagonists & inhibitors*
  • Receptors, Cell Surface / metabolism
  • Receptors, G-Protein-Coupled*
  • Urotensins / metabolism*
  • Urotensins / pharmacology*


  • (Orn8)urotensin-II
  • Ligands
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • UTS2R protein, human
  • Urotensins
  • urotensin II
  • Calcium