Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14

  • Nature. 1999 Sep 16;401(6750):282-6. doi: 10.1038/45809.
R S Ames  1 ,  H M Sarau ,  J K Chambers ,  R N Willette ,  N V Aiyar ,  A M Romanic ,  C S Louden ,  J J Foley ,  C F Sauermelch ,  R W Coatney ,  Z Ao ,  J Disa ,  S D Holmes ,  J M Stadel ,  J D Martin ,  W S Liu ,  G I Glover ,  S Wilson ,  D E McNulty ,  C E Ellis ,  N A Elshourbagy ,  U Shabon ,  J J Trill ,  D W Hay ,  E H Ohlstein ,  D J Bergsma ,  S A Douglas
Affiliations
  • 1. Department of Molecular Biology, Smith Kline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939, USA. [email protected]
PMID: 10499587 DOI: 10.1038/45809
Abstract

Urotensin-II (U-II) is a vasoactive 'somatostatin-like' cyclic peptide which was originally isolated from fish spinal cords, and which has recently been cloned from man. Here we describe the identification of an orphan human G-protein-coupled receptor homologous to rat GPR14 and expressed predominantly in cardiovascular tissue, which functions as a U-II receptor. Goby and human U-II bind to recombinant human GPR14 with high affinity, and the binding is functionally coupled to calcium mobilization. Human U-II is found within both vascular and cardiac tissue (including coronary atheroma) and effectively constricts isolated arteries from non-human primates. The potency of vasoconstriction of U-II is an order of magnitude greater than that of endothelin-1, making human U-II the most potent mammalian vasoconstrictor identified so far. In vivo, human U-II markedly increases total peripheral resistance in anaesthetized non-human primates, a response associated with profound cardiac contractile dysfunction. Furthermore, as U-II immunoreactivity is also found within central nervous system and endocrine tissues, it may have additional activities.

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