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.
Vergura
Raffaella
R
Department of Experimental and Clinical Medicine, Section of Pharmacology, University of Ferrara, via Fossato di Mortara 19, 44100 Ferrara, Italy.
Camarda
Valeria
V
Rizzi
Anna
A
Spagnol
Martina
M
Guerrini
Remo
R
Calo'
Girolamo
G
Salvadori
Severo
S
Regoli
Domenico
D
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000097:blood*; D008297:Male; D051379:Mice; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism*; D014579:Urotensins / Q000494:pharmacology*
C473469:(Orn8)urotensin-II; D043562:Receptors, G-Protein-Coupled; C121697:UTS2R protein, human; D014579:Urotensins; C029677:urotensin II