Regular Article
Identification of Urotensin II as the Endogenous Ligand for the Orphan G-Protein-Coupled Receptor GPR14

https://doi.org/10.1006/bbrc.1999.1796Get rights and content

Abstract

Urotensin II (UII) is a neuropeptide with potent cardiovascular effects. Its sequence is strongly conserved among different species and has structural similarity to somatostatin. No receptor for UII has been molecularly identified from any species so far. GPR14 was cloned as an orphan G protein-coupled receptor with similarity to members of the somatostatin/opioid receptor family. We have now demonstrated that GPR14 is a high affinity receptor for UII and designate it UII-R1a. HEK293 cells and COS-7 cells transfected with rat GPR14 showed strong, dose-dependent calcium mobilization in response to fish, frog, and human UII. Radioligand binding analysis showed high affinity binding of UII to membrane preparations isolated from HEK293 cells stably expressing rat GPR14. In situ hybridization analysis showed that GPR14 was expressed in motor neurons of the spinal cord, smooth muscle cells of the bladder, and muscle cells of the heart. The identification of the first receptor for UII will allow better understanding of the physiological and pharmacological roles of UII.

References (22)

  • D. McMaster et al.

    Peptides

    (1983)
  • T. Ichikawa et al.

    Gen. Comp. Endocrinol.

    (1984)
  • J.M. Conlon et al.

    FEBS Lett.

    (1990)
  • D. Waugh et al.

    Gen. Comp. Endocrinol.

    (1993)
  • J.M. Conlon et al.

    Regul. Pept.

    (1997)
  • D. Waugh et al.

    Gen. Comp. Endocrinol.

    (1995)
  • J.M. Conlon et al.

    Biochem. Biophys. Res. Commun.

    (1992)
  • A. Gibson et al.

    Gen. Comp. Endocrinol.

    (1986)
  • H. Itoh et al.

    Eur. J. Pharmacol.

    (1988)
  • A. Marchese et al.

    Genomics

    (1995)
There are more references available in the full text version of this article.

Cited by (0)

1

To whom correspondence should be addressed. Fax: (215)652-2075. E-mail: [email protected].

View full text