Urantide mimics urotensin-II induced calcium release in cells expressing recombinant UT receptors

Eur J Pharmacol. 2004 Sep 13;498(1-3):83-6. doi: 10.1016/j.ejphar.2004.07.089.

Abstract

Urotensin-II is the natural ligand of the UT receptor. This novel system is involved in the regulation of cardiovascular functions. Recently, a urotensin-II analog ([Pen5,DTrp7,Orn8]urotensin-II(4-11)) named urantide, has been proposed as a selective and potent UT receptor antagonist. In order to pharmacologically characterize this new compound, urantide was tested on the native UT receptors of the rat aorta and on the human recombinant receptors expressed in CHO cells (CHO(hUT)). Indeed, urantide behaves as a competitive, potent (pA2 8.24), and pure antagonist in the rat aorta bioassay, while as an agonist (pEC50 8.11) in a calcium mobilization assay performed in CHO(hUT) cells. Urantide should be considered a low efficacy partial agonist.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / physiology
  • CHO Cells
  • Calcium / metabolism*
  • Cricetinae
  • Cricetulus
  • DNA, Recombinant / genetics
  • Dose-Response Relationship, Drug
  • Gene Expression
  • In Vitro Techniques
  • Male
  • Peptide Fragments / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / physiology*
  • Urotensins / pharmacology*
  • Vasoconstriction / drug effects

Substances

  • DNA, Recombinant
  • Peptide Fragments
  • Receptors, G-Protein-Coupled
  • UTS2R protein, human
  • Urotensins
  • urotensin II (4-11), Pen(5)-Trp(7)-Orn(8)-
  • urotensin II
  • Calcium