Urotensin II stimulates plasma extravasation in mice via UT receptor activation

The peptide urotensin II (U-II) is the cognate ligand of the G-protein coupled receptor UT (formerly GPR14). A role in the regulation of cardiovascular functions has been proposed for this novel peptide/receptor system. In the present study, we evaluated the ability of U-II to induce plasma extravasation in mice and attempted to characterize the receptor involved using the novel UT receptor ligand, [Orn(8)]U-II. The Evans blue technique was used to quantify plasma extravasation. U-II (0.01, 0.1, 1 and 10 nmol/kg) dose-dependently stimulated plasma extravasation in airways, gastrointestinal and urogenital tract tissues from mice, but not in the skin. In most tissues, the dose/response curves to U-II were bell shaped with the maximal effect induced by 1 nmol/kg. [Orn(8)]U-II at 30 nmol/kg was per se either inactive or produced a non-significant increase in plasma extravasation; in the presence of 30 nmol/kg [Orn(8)]U-II, the effects of 1 nmol/kg U-II were always reduced and, in some tissues, abolished. The present findings demonstrate that U-II promotes plasma extravasation in various mouse vascular regions via activation of UT receptors. The mouse plasma extravasation assay will be a useful tool in future studies aimed at characterizing the pharmacological features of novel UT receptor ligands in vivo.