Urotensin II is the endogenous ligand of a G-protein-coupled orphan receptor, SENR (GPR14).

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 EC(50) 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.

[1]  H. Vaudry,et al.  Somatostatin- and urotensin II-related peptides: molecular diversity and evolutionary perspectives , 1997, Regulatory Peptides.

[2]  D. Grandy,et al.  Orphanin FQ: A Neuropeptide That Activates an Opioidlike G Protein-Coupled Receptor , 1995, Science.

[3]  N. Hazon,et al.  Distribution and molecular forms of urotensin II and its role in cardiovascular regulation in vertebrates. , 1996, The Journal of experimental zoology.

[4]  D. Richter,et al.  Identification of melanin concentrating hormone (MCH) as the natural ligand for the orphan somatostatin‐like receptor 1 (SLC‐1) , 1999, FEBS letters.

[5]  Hirokazu Matsumoto,et al.  A prolactin-releasing peptide in the brain , 1998, Nature.

[6]  Marc Parmentier,et al.  Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor , 1995, Nature.

[7]  H. Sarau,et al.  Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14 , 1999, Nature.

[8]  Yumiko Saito,et al.  Molecular characterization of the melanin-concentrating-hormone receptor , 1999, Nature.

[9]  H. Bern,et al.  Cardiovascular effects of urotensin II in anesthetized and pithed rats. , 1986, General and comparative endocrinology.

[10]  O. Nishimura,et al.  Isolation and identification of melanin-concentrating hormone as the endogenous ligand of the SLC-1 receptor. , 1999, Biochemical and biophysical research communications.

[11]  H. Itoh,et al.  Functional receptors for fish neuropeptide urotensin II in major rat arteries. , 1988, European journal of pharmacology.

[12]  Jilly F. Evans,et al.  Receptor for motilin identified in the human gastrointestinal system. , 1999, Science.

[13]  H. Heng,et al.  Cloning and chromosomal mapping of three novel genes, GPR9, GPR10, and GPR14, encoding receptors related to interleukin 8, neuropeptide Y, and somatostatin receptors. , 1995, Genomics.

[14]  A. Gibson.  Complex effects of Gillichthys urotensin II on rat aortic strips , 1987, British journal of pharmacology.

[15]  J. Chambers,et al.  Melanin-concentrating hormone is the cognate ligand for the orphan G-protein-coupled receptor SLC-1 , 1999, Nature.

[16]  E. Grazzini,et al.  The receptor for the orexigenic peptide melanin-concentrating hormone is a G-protein-coupled receptor , 1999, Nature Cell Biology.

[17]  D. Bergsma,et al.  Orphan G protein-coupled receptors: a neglected opportunity for pioneer drug discovery. , 1997, Trends in pharmacological sciences.

[18]  T. Deguchi,et al.  Cloning and sequence analysis of cDNAs encoding precursors of urotensin II-alpha and -gamma , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[19]  D. Thompson,et al.  A novel putative neuropeptide receptor expressed in neural tissue, including sensory epithelia. , 1995, Biochemical and biophysical research communications.

[20]  S. Hinuma,et al.  Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. , 1998, Biochemical and biophysical research communications.

[21]  B. Lowell,et al.  Mice lacking melanin-concentrating hormone are hypophagic and lean , 1998, Nature.

[22]  K. Lukowiak,et al.  Distribution and coexistence of urotensin I and urotensin II peptides in the cerebral ganglia of Aplysia californica , 1992, Peptides.

[23]  S. Carr,et al.  Orexins and Orexin Receptors: A Family of Hypothalamic Neuropeptides and G Protein-Coupled Receptors that Regulate Feeding Behavior , 1998, Cell.