2. Academic Validation
  3. Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14

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

Affiliation

  • 1 Department of Molecular Biology, Smith Kline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939, USA. bobvames1@sbphrd.com
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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