Desensitisation of native and recombinant human urotensin-II receptors

Naunyn Schmiedebergs Arch Pharmacol. 2009 Nov;380(5):451-7. doi: 10.1007/s00210-009-0441-9. Epub 2009 Aug 13.


Human urotensin-II (U-II) is an 11-amino-acid cyclic peptide that activates a G(q)-coupled receptor named UT. Little is known about the desensitisation profile of this receptor as peptide binding is essentially irreversible. In the present study, we have examined the effects of U-II and carbachol on Ca(2+) signalling in SJCRH30 rhabdomyosarcoma (receptor density, B(max) approximately 0.1 pmol/mg protein) and human embroynic kidney (HEK)(hUT) (B(max) approximately 1.4 pmol/mg protein) cells expressing native and recombinant UT, respectively. In SJCRH30, HEK(hUT) and human peripheral blood mononuclear cells induced to express native UT by treatment with 2 microg/ml lipopolysaccharide (LPS), we have measured the effects of U-II treatment on UT mRNA. In SJCRH30 cells, primary stimulation with carbachol (250 microM) did not affect a secondary challenge with U-II (1 microM) and primary challenge with U-II did not affect a secondary challenge with carbachol. In contrast, in HEK(hUT) cells, primary stimulation with carbachol (250 microM) reduced a secondary challenge to U-II (1 microM) by 84% and primary challenge with U-II reduced a secondary challenge to carbachol by 76%. Pre-treatment of SJCRH30 cells with U-II reduced UT mRNA after 6 h and this returned to basal after 24 h. In recombinant HEK(hUT) cells, UT mRNA expression increased following a 6 h treatment with 1 microM U-II. U-II treatment of naïve un-stimulated peripheral blood mononuclear cells was without effect. However, when UT expression is up-regulated following 15 h of LPS treatment, a 6 h U-II challenge reduced UT mRNA by 66%. In summary, we report differences in the desensitisation profiles of native and recombinant U-II receptors. Design and interpretation of functional experiments are hampered by irreversibility of U-II binding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Calcium Signaling / drug effects
  • Carbachol / pharmacology*
  • Cell Line
  • Cell Line, Tumor
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Lipopolysaccharides
  • Middle Aged
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism*
  • Receptors, G-Protein-Coupled / metabolism*
  • Recombinant Proteins / metabolism
  • Rhabdomyosarcoma / metabolism
  • Urotensins / pharmacology*


  • Lipopolysaccharides
  • RNA, Messenger
  • Receptors, G-Protein-Coupled
  • Recombinant Proteins
  • UTS2R protein, human
  • Urotensins
  • Carbachol
  • urotensin II