Renal and vascular actions of urotensin II.
The peptide hormone urotensin II (UII) has been highly conserved through the vertebrates from fish to humans. As it was shown to be the endogenous ligand for the mammalian orphan G-protein-coupled receptor GPR14, now renamed the UT receptor, interest in UII physiology has grown. Initial observations of a potent vasoconstrictor effect have been tempered with the subsequent revelation of an endothelium-dependent vasodilator action. These complex and contrasting vascular actions are both species- and vascular bed-specific. UII also plays a role in body fluid regulation in lower vertebrates, and it now appears that this extends to mammals. The kidney is a major source of both circulating and urinary UII. UII is found in both the proximal tubules and collecting ducts; the UT receptor is localized primarily to the renal medulla, with greatest expression in the inner medullary collecting ducts. Infusion in rats produced conflicting results: exogenous UII has been shown to increase glomerular filtration rate (GFR) and excretion of water and sodium, but also to reduce the same variables. Inhibition of UT receptor activity with the antagonist urantide resulted in an increase in GFR, diuresis, and natriuresis, suggesting that endogenous UII exerts a tonic influence on basal renal function. UII may also play a role in renal disease, being elevated in the circulation or urine of patients with renal failure and in experimental models of cardiovascular disease such as the spontaneously hypertensive rat. It remains to be established whether these changes represent an underlying primary cause or a compensatory response.
Ashton
N
N
Faculty of Life Sciences, University of Manchester, Manchester, UK. nick.ashton@manchester.ac.uk
D000595:Amino Acid Sequence; D000818:Animals; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000502:physiology; D007674:Kidney Diseases / Q000235:genetics / Q000503:physiopathology; D008969:Molecular Sequence Data; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014579:Urotensins / Q000032:analysis / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
D043562:Receptors, G-Protein-Coupled; C121697:UTS2R protein, human; D014579:Urotensins; C473142:Uts2r protein, rat; C029677:urotensin II