Role of urotensin II and its receptor in health and disease

Abstract

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.

International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, Urotensin II–Related Peptide, and Their Receptor: From Structure to Function

“…In the cardiovascular system, UII mRNA is expressed in vascular smooth muscle cells , endothelial cells McDonald et al, 2007), and cardiac fibroblasts (Tzanidis et al, 2003). In the human heart, UII mRNA is found in the right atrium and ventricular septum (Matsushita et al, 2001).…”

“…IP 3 can then bind to its receptors on endoplasmic/sarcoplasmic reticula, causing the increase in intracellular Ca 2+ underlying contraction (see section III.B). In the endothelium-mediated vasodilation caused by UII, UT activation on the endothelium leads to the release of NO and endothelium-derived hyperpolarizing factor, causing vasodilation (McDonald et al, 2007). Differences in expression of UT in vessels of different sizes and locations may also contribute to the variability in response to UII (Onan et al, 2004a).…”

The Importence of Urotensin and Urotensin Receptors in Cardiovascular System

“…Sağlıklı insandaki infüzyon çalışmalarında ÜT 2'nin çok küçük bir role sahip olduğunun gösterildiği belirtilmiş, hastalık durumlarında ise nispeten rolunun daha belirgin olduğuna değinilmiş-tir [25]. ÜT 2 potent hemodinamik olaylarda [25], pozitif inotrop ve kronotrop yanıtlarda [26], osmoregulatuar olaylarda [27], kollajen ve fibronektin birikimini indüklemede [28,29], inflamatuar yanıt modülasyonunda [30], kardiyak ve vasküler hipertrofide [31] rol oynar. ÜT 2 aynı zamanda güçlü anjiojenik etkiye neden olur [32,33].…”

“…Bu yüzden ürotensiner-jik sistem kalp yetmezliği, hipertansiyon, preeklampsi, diyabet, böbrek ve karaciğer hastalıkları, varis kanaması, ülserler, psikolojik ve nörolojik hastalıklarla ilişkilendirilmiştir [6]. ÜT 2 konsantrasyonlarının kalp yetmezliği, renal disfonksiyon, diyabet ve karaciğer yetmezliğinde yükseldiği belirtilmiş [25], ÜT 2'nin kardiyovasküler hastalıklarda, aterosklerozda, diyabette, renal disfonksiyon ve hipertansyionda yükseldiğine de deyinilmiştir [34]. ÜT 2'nin plazma konsantrasyonu sağlıklı kişilerde sürekli olarak düşük bulunmaktadır, normal şartlar altında dolaşımda bulunan bir hormon değildir.…”

Evaluation of serum urotensin-II levels of children with attention deficit hyperactivity disorder and autism spectrum disorder

“…Stimulation of the U-II via receptor's phosphorinositide cycle causes an influx of Ca +2 into the cells, thus increasing the levels of intracellular Ca +2 . 12 Vascular endothelial cells, the myocardium, smooth muscle cells, adrenal tissues, the thyroid, and the renal cortex are known to have U-II receptors. 13 In animal studies, U-II has been found in the central nervous system, the cerebral cortex, the amygdala, the hippocampus, the nucleus accumbens, the thalamus, and the striatum.…”