Human urotensin II mediates vasoconstriction via an increase in inositol phosphates.
The cyclic peptide urotensin II has recently been cloned from human and reported to potently constrict primate blood vessels. To elucidate the cellular signalling mechanisms of this peptide, we investigated a possible relationship of vasomotor effects of human urotensin II and phosphoinositide turnover in isolated rabbit thoracic aorta. Human urotensin II produced a slowly developing increase in isometric contractile force (pEC(50)=9.0) that was endothelium-independent. The contractile effect of urotensin II was significantly inhibited by the phospholipase C inhibitor, 2-nitro-4-carboxyphenyl-N,N,-diphenylcarbamate (NCDC), but not by the cyclooxygenase inhibitor, indomethacin. In slices of rabbit thoracic aorta, human urotensin II increased 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 the 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 receptor.
Saetrum Opgaard
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Department of Pharmacology, College of Medicine, 360 Med Surge II, University of California-Irvine, 92697-4625, Irvine, CA, USA. osaetrum@uci.edu
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D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D002219:Carbamates / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D008297:Male; D048448:Phenylcarbamates; D010716:Phosphatidylinositols / Q000378:metabolism*; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000502:physiology; D043562:Receptors, G-Protein-Coupled; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000502:physiology; D014579:Urotensins / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D002219:Carbamates; D048448:Phenylcarbamates; D010716:Phosphatidylinositols; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C121697:UTS2R protein, human; D014579:Urotensins; C025508:2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate; C029677:urotensin II; D010738:Type C Phospholipases