[Orn5]URP acts as a pure antagonist of urotensinergic receptors in rat cortical astrocytes

Peptides. 2008 May;29(5):813-9. doi: 10.1016/j.peptides.2007.10.023. Epub 2007 Nov 6.


Cultured rat astrocytes, which express functional urotensin II (UII)/UII-related peptide (URP) receptors (UT), represent a very suitable model to investigate the pharmacological profile of UII and URP analogs towards native UT. We have recently designed three URP analogs [D-Trp4]URP, [Orn5]URP and [D-Tyr6]URP, that act as UT antagonists in the rat aortic ring bioassay. However, it has been previously reported that UII/URP analogs capable of inhibiting the contractile activity of UII possess agonistic activity on UT-transfected cells. In the present study, we have compared the ability of URP analogs to compete for [125 I]URP binding and to modulate cytosolic calcium concentration ([Ca2+]c) in cultured rat astrocytes. All three analogs displaced radioligand binding: [D-Trp4]URP and [D-Tyr6]URP interacted with high- and low-affinity sites whereas [Orn5]URP only bound high-affinity sites. [D-Trp4]URP and [D-Tyr6]URP both induced a robust increase in [Ca2+]c in astrocytes while [Orn5]URP was totally devoid of activity. [Orn5]URP provoked a concentration-dependent inhibition of URP- and UII-evoked [Ca2+]c increase and a rightward shift of the URP and UII dose-response curves. The present data indicate that [D-Trp4]URP and [D-Tyr6]URP, which act as UII antagonists in the rat aortic ring assay, behave as agonists in the [Ca2+]c mobilization assay in cultured astrocytes, whereas [Orn5]URP is a pure selective antagonist in both rat aortic ring contraction and astrocyte [Ca2+]c mobilization assays.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Astrocytes / cytology
  • Astrocytes / metabolism*
  • Calcium / metabolism
  • Cells, Cultured
  • Cerebral Cortex / cytology*
  • Peptide Hormones* / chemistry
  • Peptide Hormones* / metabolism
  • Radioligand Assay
  • Rats
  • Receptors, G-Protein-Coupled / antagonists & inhibitors*
  • Receptors, G-Protein-Coupled / metabolism
  • Urotensins / genetics
  • Urotensins / metabolism*


  • Peptide Hormones
  • Receptors, G-Protein-Coupled
  • Urotensins
  • Uts2r protein, rat
  • urotensin II-related peptide, rat
  • urotensin II
  • Calcium