Urotensin II (UII) is the most potent vasoconstrictor known to date. The scientists at Takeda Chemical Industries in Japan recently reported the identification of the endogenous ligand for urotensin II. Using goby UII antibody, immunoreactivity experiments led to the detection of this new peptide in rat brains1. Its primary structure resembled urotensin II (UII), therefore, the new isolated ligand was named urotensin II-related peptide (URP).
The cDNA sequence of rat was determined to possess a potential dibasic flanking cleavage site at the amino terminus. Subsequent studies showed that human and mouse URPs are in fact identical to rat URP. This newly identified peptide exhibits the following activity:
- High affinity, saturable binding activity to human and rat UII receptors (UIIR), Kd = 170 pM and 91 pM, respectively
- Ca2+ mobilization activity reported in CHO cells expressing human or rat UIIR with ED50 = 4.8 nM (human UIIR) and 0.55 nM (rat UIIR)
- Long-lasting, hypotensive effect in anaesthetized rat at 10 nmol/kg dosage levels
While tissue distribution of preproURP is abundant in both human and rat, not only is distribution different in both but it also is distinct from that of urotensin II. This new discovery should aid structure elucidation studies of urotensin peptides and help lead to new approaches in hypertension research.