Human urotensin-II as a novel cardiovascular target: 'heart' of the matter or simply a fishy 'tail'?

Urotensin-II (U-II), originally identified as a fish neuropeptide, exerts a broad spectrum of biological actions in mammals: responses that influence cardiorenal, pulmonary (bronchoconstriction), central nervous system (locomotion) and endocrine (thyroid-stimulating hormone, prolactin and insulin secretion) function. Because the U-II isopeptide family is highly conserved across species, both amongst invertebrates and vertebrates, it has been inferred that U-II and its G-protein-coupled receptor, UT, play a seminal role in the physiological regulation of major mammalian organ systems, most notably within the cardiovasculature. However, despite the evolutionary conservation of U-II, the (patho)physiological significance of this 'somatostatin-like' peptide remains ambiguous. Can the identification of a fish peptide as a ligand for an 'orphan' mammalian G-protein-coupled receptor really tell us something about human physiology? Emerging preclinical and clinical data suggest that it might.