Role of urotensin II and its receptor in health and disease.
Urotensin II (U-II) is currently the most potent vasoconstrictor identified. This action is brought about via activation of a G(q/11)-protein coupled receptor (UT receptor). U-II activation of the UT receptor increases inositol phosphate turnover and intracellular Ca(2+). In addition to producing vasoconstriction, dilation and ionotropic effects have also been described. There is considerable variation in the responsiveness of particular vascular beds from the same and different species, including humans. Receptors for U-II are located peripherally on vascular smooth muscle (contractile responses) and endothelial cells (dilatory responses via nitric oxide). In humans, plasma U-II is elevated in heart failure, renal failure, liver disease, and diabetes. Iontophoresis of U-II in healthy volunteers produces vasodilation (of the forearm) while in patients with heart failure or hypertension a constriction is observed. To date there is only one clinical study using a UT receptor antagonist (palosuran) in diabetic patients with macroalbuminuria. This antagonist reduced albumin excretion, probably by increasing renal blood flow. Studies in other disease conditions are eagerly awaited. In summary, the U-II / UT receptor system has clinical potential, and for the anesthesiologist, this novel peptide-receptor system may be of use in the intensive care unit.
Department of Cardiovascular Sciences, Pharmacology and Therapeutics Group, Division of Anaesthesia, Critical Care and Pain Management, University of Leicester, LRI, Leicester, LE1 5WW, UK.
John
J
McDonald
Madura
M
Batuwangala
David G
DG
Lambert
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D006224:Cricetinae; D003412:Cricetulus; D003920:Diabetes Mellitus / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051437:Renal Insufficiency / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology; D014579:Urotensins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D047908:Intracellular Signaling Peptides and Proteins; D011804:Quinolines; D043562:Receptors, G-Protein-Coupled; C121697:UTS2R protein, human; D014579:Urotensins; D014508:Urea; C029677:urotensin II; D002118:Calcium; C493249:1-(2-(4-benzyl-4-hydroxypiperidin-1-yl)ethyl)-3-(2-methylquinolin-4-yl)urea