Role of urotensin II in health and disease

Abstract

Urotensin II (UII) is an 11 amino acid cyclic peptide originally isolated from the goby fish. The amino acid sequence of UII is exceptionally conserved across most vertebrate taxa, sharing structural similarity to somatostatin. UII binds to a class of G protein-coupled receptor known as GPR14 or the urotensin receptor (UT). UII and its receptor, UT, are widely expressed throughout the cardiovascular, pulmonary, central nervous, renal, and metabolic systems. UII is generally agreed to be the most potent endogenous vasoconstrictor discovered to date. Its physiological mechanisms are similar in some ways to other potent mediators, such as endothelin-1. For example, both compounds elicit a strong vascular smooth muscle-dependent vasoconstriction via Ca 2ϩ release. UII also exerts a wide range of actions in other systems, such as proliferation of vascular smooth muscle cells, fibroblasts, and cancer cells. It also 1) enhances foam cell formation, chemotaxis of inflammatory cells, and inotropic and hypertrophic effects on heart muscle; 2) inhibits insulin release, modulates glomerular filtration, and release of catecholamines; and 3) may help regulate food intake and the sleep cycle. Elevated plasma levels of UII and increased levels of UII and UT expression have been demonstrated in numerous diseased conditions, including hypertension, atherosclerosis, heart failure, pulmonary hypertension, diabetes, renal failure, and the metabolic syndrome. Indeed, some of these reports suggest that UII is a marker of disease activity. As such, the UT receptor is emerging as a promising target for therapeutic intervention. Here, a concise review is given on the vast physiologic and pathologic roles of UII.UT receptor; somatostatin; human; experimental animals; autocrine/paracrine UROTENSIN II (UII) was initially isolated from the urophysis of the goby fish (Gillichthys mirabilis) (97). The peptide was subsequently isolated from the white sucker (Catostomus commersoni) and the carp (Cyprinus carpio). Although there were variations in the amino acid sequence near the amino terminus, in both species the UII molecule retained the COOH-terminal cyclic sequence: -Cys

Pressor and renal regional hemodynamic effects of urotensin II in neonatal pigs

“…Data are expressed as meanGS.E.M. AngII and losartan were co-administered to the piglets w10 min after intrarenal arterial bolus injection of losartan Ross et al 2010, Tsoukas et al 2011. However, the cyclic hexapeptide sequence in UII carboxyl-terminus, which is responsible for its biological activity, is highly conserved between species (Itoh et al 1987, Conlon et al 1990, Coulouarn et al 1998, Douglas et al 2004.…”

“…These results raise the possibility that the hypotensive effect of urantide may be due to its systemic but not localized renal vasoregulatory actions. Neurons of the brain and spinal cord express UII (Coulouarn et al 1998, Douglas et al 2004, Ross et al 2010. Studies have also shown that UII can modulate cardiovascular homeostasis via central neural mechanisms (Gibson et al 1986, Lu et al 2002, Lin et al 2003.…”

“…Alterations in UII and UII receptor (UTR) expression and plasma and urinary UII concentrations have been associated with renal dysfunctions, including hypertensive renal disease, diabetic nephropathy, glomerulonephritis, and renal tubular diseases (Matsushita et al 2001, Douglas et al 2004, Langham et al 2004, Ashton 2006, Balat et al 2007, Ross et al 2010. However, the physiological role of UII in the kidney remains controversial with studies reporting attenuation and elevation of important renal parameters, including total renal blood flow (RBF), glomerular filtration rate (GFR), urine flow rate (UV), and urinary sodium (U Na V) and potassium (U K V) excretion (Zhang et al 2003, Ovcharenko et al 2006, Song et al 2006, Abdel-Razik et al 2008a,b, Shi et al 2008.…”

MOLECULAR EVOLUTION OF GPCRS: Somatostatin/urotensin II receptors

“…All functional data relate to UTS2R1, the single UTS2R receptor present in placental mammals, as the other UTS2R isoforms have only been obtained recently. UTS2R1 was originally described as being coupled to Gq, but other signal transduction pathways involving G s and G i have subsequently been identified, associated with multiple signaling cascades (Ross et al 2010).…”

Study the Role of Urotensin Ii as a Predictor for Hepatorenal Syndrome

“…Evidence points to the vasodilatation theory as a more tangible explanation for the development of HRS. Urotensin II (U II) is a somatostatinlike cyclic peptide, its vascular tone both species specific and diseases specific [6]. Urotensin II interfere with sympathetic and nitric oxide (NO) system [7].…”