Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14 - PubMed (original) (raw)
. 1999 Sep 16;401(6750):282-6.
doi: 10.1038/45809.
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
- PMID: 10499587
- DOI: 10.1038/45809
Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14
R S Ames et al. Nature. 1999.
Erratum in
- Nature 1999 Dec 23-30;402(6764):898
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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