Regular Article
Urotensin II Is the Endogenous Ligand of a G-Protein-Coupled Orphan Receptor, SENR (GPR14)

https://doi.org/10.1006/bbrc.1999.1640Get rights and content

Abstract

Two molecular species of urotensin II (UII) were isolated from porcine spinal cords and identified as the endogenous ligands of a G-protein-coupled orphan receptor, SENR (sensory epithelium neuropeptide-like receptor), which is identical to GPR14. We established a CHO cell line stably expressing the rat SENR and investigated several tissue extracts to evoke the response mediated by the SENR. Extract from porcine spinal cords showed an activity of arachidonic acid metabolites release from SENR-expressing cells and was purified using HPLC. Two active substances were isolated and their sequences were determined as GPTSECFWKYCV and GPPSECFWKYCV, which were revealed to be porcine UII. Synthetic UII peptides caused arachidonic acid metabolites release activity in the rat SENR-expressing cells with an EC50 value of 1 nM. Three cDNAs encoding the precursor proteins of porcine UII were cloned from a porcine spinal cord cDNA library; 2 consist of 121 amino acid residues and the other, which seemed to be a splicing variant, consist of 85 residues.

References (27)

  • J.M. Stadel et al.

    Trends Pharmacol. Sci.

    (1997)
  • T. Sakurai et al.

    Cell

    (1998)
  • K. Tatemoto et al.

    Biochem. Biophys. Res. Commun.

    (1998)
  • Y. Shimomura et al.

    Biochem. Biophys. Res. Commun.

    (1999)
  • D. Bachner et al.

    FEBS Lett.

    (1999)
  • M. Tal et al.

    Biochem. Biophys. Res. Commun.

    (1995)
  • A. Marchese et al.

    Genomics

    (1995)
  • S. Hinuma et al.

    Bichim. Biophys. Acta

    (1994)
  • J.M. Conlon et al.

    Regul. Pept.

    (1997)
  • G.C. Gonzalez et al.

    Peptide

    (1992)
  • A. Gibson et al.

    Gen. Comp. Endocrinol.

    (1986)
  • H. Itoh et al.

    Eur. J. Pharmacol.

    (1988)
  • J.-C. Meunier et al.

    Nature

    (1995)
  • Cited by (197)

    • Identification and signaling characterization of four urotensin II receptor subtypes in the western clawed frog, Xenopus tropicalis

      2020, General and Comparative Endocrinology
      Citation Excerpt :

      Previous studies on the signaling cascade via a single UTR (UTR1) in mammals showed that UTR1 is linked to three G proteins (Gq, Gi/o, and G12/13) in various tissues and cells. UTR was originally found to primarily activate the phospholipase C (PLC)/ protein kinase C (PKC) pathway, coupled to Gq protein (Filipeanu et al., 2002; Mori et al., 1999; Nothacker et al., 1999). UTR activation with UII increases phosphoinositide turnover and induces mobilization of Ca2+ from intracellular stores (Song et al., 2006; Filipeanu et al., 2002; Gibson et al., 1988).

    • Blocking of urotensin receptors as new target for treatment of carrageenan induced inflammation in rats

      2016, Peptides
      Citation Excerpt :

      Latest studies demonstrated that U-II modulates its effects via U-II receptors also known as GPR14 that are G-protein coupled receptors on cell membrane [5]. UTR was discovered by 4 groups simultaneously [9–11]. Studies showed widespread expression of U-II receptors in cardiovascular, pulmonary, central nervous, renal and metabolic systems and especially in inflammatory regions [12–14].

    View all citing articles on Scopus

    Abbreviations used: UII, urotensin II; SENR, sensory epithelium neuropeptide-like receptor; EC50, median effective concentration; GPCR, G-protein-coupled receptor; TFA, trifluoroacetic acid.

    1

    Corresponding author. Fax: +81-298-64-5000. E-mail: [email protected].

    View full text