Urotensin II (Rat)

[Potent Vasoconstrictor]

Urotensin II (U-II) is a disulfide-linked small peptide initially isolated from fish urophysis. Subsequently, the cDNA sequence encoding the human U-II precursor was determined, and the corresponding mRNA was found to exist predominantly in spinal cord [Proc. Natl. Acad. Sci. USA, 95, 15803 (1998)]. Human U-II, then, was revealed to be an agonist for the orphan receptor GPR14 and exerts a strong vasoconstricting activity in the isolated thoracic aorta of rat [Nature, 401, 282 (1999)]. 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.

Following the sequence determination of human U-II, the same group reported the corresponding rat peptide cDNA sequence [FEBS Lett., 457, 28 (1999)]. When we look at the deduced peptide sequence of rat prepro-U-II, there are two double basic sites at its C-terminal region, which might be the enzymatic cleavage sites for yielding the mature peptide of rat U-II. We chose the shorter peptide of 14 amino acid residues with pyroglutamic acid modification for Gln¹¹⁰ as the possible candidate for rat U-II and chemically synthesized it. Synthetic [Pyr¹¹⁰]-prepro-U-II (110-123) was confirmed to have a vasoconstricting activity as potent as that of human peptide in the isolated thoracic aorta of rat (unpublished result). Therefore, we tentatively named this peptide rat U-II in our catalog, although the mature form of rat U-II remains to be determined. Recently, Davenport AP & Maguire JJ have predicted the sequence of rat or mouse U-II as prepro-U-II (110-123) [Trends Pharmacol. Sci., 21, 80 (2000)].