Urotensin II stimulates plasma extravasation in mice via UT receptor activation.

Abstract The peptide urotensin II (U-Il) is the cognate ligand of the 6-protein coupled receptor UT (formerly GPRI4). 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-Il to induce plasma extravasation in mice and attempted to characterize the receptor involved using the novel UT receptor ligand, [Orn⁸] U-Il. The Evans blue technique was used to quantify plasma extravasation. U-Il (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-Il were bell shaped with the maximal effect induced by I nmol/kg. [Orn⁸]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 [Orn⁸]U-II, the effects of I nmol/kg U-Il were always reduced and, in some tissues, abolished. The present findings demonstrate that U-Il 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. [ABSTRACT FROM AUTHOR]