Urotensin II: Better than somatostatin for portal hypertension?

Urotensin-II (U-II) is a vasoactive 'somatostatin-like' cyclic peptide whic h was originally isolated from fish spinal cords, and which has recently be en cloned from man. Here we describe the identification of an orphan human G-protein-coupled receptor homologous to rat GPR14 and expressed predominan tly 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 bind ing is functionally coupled to calcium mobilization. Human U-II is found wi thin both vascular and cardiac tissue (including coronary atheroma) and eff ectively constricts isolated arteries from non-human primates. The potency of vasoconstriction of U-II is an order of magnitude greater than that of e ndothelin-1, making human U-II the most potent mammalian vasoconstrictor id entified so far. In vivo, human U-II markedly increases total peripheral re sistance in anaesthetized non-human primates, a response associated with pr ofound cardiac contractile dysfunction. Furthermore, as U-II immunoreactivi ty is also found within central nervous system and endocrine tissues, it ma y have additional activities.