Human urotensin II mediates vasoconstriction via an increase in inositol phosphates

The cyclic peptide urotensin LI has recently been cloned from human and rep orted to potently constrict primate blood vessels. To elucidate the cellula r signalling mechanisms of this peptide, we investigated a possible relatio nship of vasomotor effects of human urotensin II and phosphoinositide turno ver in isolated rabbit thoracic aorta. Human urotensin II produced a slowly developing increase in isometric contractile force (pEC(50) = 9.0) that wa s endothelium-independent. The contractile effect of urotensin II was signi ficantly inhibited by the phospholipase C inhibitor, 2-nitro-4-carboxypheny l-N,N,-diphenylcarbamate (NCDC), but not by the cyclooxygenase inhibitor, i ndomethacin. In slices of rabbit thoracic aorta, human urotensin II increas ed phosphoinositide hydrolysis, and this effect was also inhibited by NCDC. The potency of urotensin II (pEC(50) = 8.6) was similar to that found in t he contractile studies. Thus, vasoconstrictor effects of human urotensin II appear to be mediated by a phospholipase C-dependent increase in inositol phosphates, suggesting that the peptide acts via a G(q) protein-coupled rec eptor. (C) 2000 Elsevier Science B.V. All rights reserved.