Urotensin II-related peptide, the endogenous ligand for the urotensin II receptor in the rat brain.
Urotensin II (UII) is a piscine neuropeptide originally isolated from the teleost urophysis. The existence of UII in mammals has been demonstrated by cloning of the mammalian orthologs of UII precursor protein genes. While rat and mouse orthologs have been reported, only the tentative structures of UII peptides of these animals have been demonstrated, since prepro-UII proteins lack the typical processing sites in the amino-terminal region of the mature peptides. A novel peptide, UII-related peptide (URP), was discovered by monitoring UII-immunoreactivity in the rat brain, and its amino acid sequence was determined to be ACFWKYCV. cDNAs encoding rat, mouse, and human precursor proteins for URP were cloned and showed that the sequences of mouse and human URP peptides are identical to that for rat URP. URP was found to bind and activate the human or rat urotensin II receptors [GPR14, UT receptor (UTR)] and showed a hypotensive effect when administrated to anesthetized rats. The prepro-URP gene is expressed in several rat tissues, although with lower levels than the prepro-UII gene and, in the human, is expressed comparably to prepro-UII in several tissues except the spinal cord. These results suggest that URP is the endogenous and functional ligand for urotensin II receptor in the rat and mouse, and possibly in the human.
Discovery Research Laboratories, Pharmaceutical Research Division, Takeda Chemical Industries Ltd., Wadai 10, Tsukuba, Ibaraki 300-4293, Japan. mori_masaaki@takeda.co.jp
Masaaki
M
Mori
Masahiko
M
Fujino
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000502:physiology*; D003001:Cloning, Molecular; D017124:Conserved Sequence; D006801:Humans; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D036361:Peptide Hormones / Q000235:genetics / Q000502:physiology*; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D008024:Ligands; D036361:Peptide Hormones; D043562:Receptors, G-Protein-Coupled; C473142:Uts2r protein, rat; C479081:urotensin II-related peptide, rat