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


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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@article{Ames1999HumanUI, title={Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14.}, author={Robert S. Ames and Henry M. Sarau and Jon Chambers and Robert N. Willette and Nambi V Aiyar and Anne M. Romanic and Calvert S. Louden and James R. J. Foley and Charles F Sauermelch and Robert W. Coatney and Zhaohui Ao and Jyoti Disa and Steve D. Holmes and Jeffrey M . Stadel and Jessica D. Martin and Wen Sheng Liu and G I Glover and Sue Wilson and Dustin E. McNulty and Christopher E. Ellis and Nabil A. Elshourbagy and Usman Shabon and John J. Trill and Douglas W. P. Hay and Eliot H. Ohlstein and Derk J. Bergsma and Stephen A. Douglas}, journal={Nature}, year={1999}, volume={401 6750}, pages={282-6} }