Disease relevance of Uts2

• Urotensin II promotes hypertrophy of cardiac myocytes via mitogen-activated protein kinases [1].
• The exposure of cultured cardiomyocytes from neonatal rats to UII dose-dependently activated extracellular signal-regulated kinases (ERKs), important molecules in the development of cardiac hypertrophy [2].
• Urotensin-II (U-II), the most potent mammalian vasoconstrictor identified, and its receptor, UT, exhibits increased expression in cardiac tissue and plasma in congestive heart failure (CHF) patients [3].
• These results suggest that central urotensin II may play a role in the pathogenesis of hypertension in SHR [4].
• The aim of this study was to investigate the alteration of micro- and ultrapathologic structure, gaseous molecules, and U-II in rats with pulmonary hypertension induced by increased pulmonary blood flow [5].

Psychiatry related information on Uts2

• Urotensin II modulates rapid eye movement sleep through activation of brainstem cholinergic neurons [6].

High impact information on Uts2

• In this model system, urotensin II promoted strong hypertrophic growth and phenotypic changes, including cell enlargement and sarcomere reorganization [1].
• BACKGROUND: It has been shown that central urotensin II acts on the central nervous system to increase arterial pressure in conscious rats [7].
• OBJECTIVE: To investigate the intracellular signal transduction mechanisms of the central cardiovascular action of urotensin II [7].
• RESULTS: I.c.v. injection of urotensin II increased both arterial pressure and heart rate (14.9 +/-1.5 mmHg and 94.6 +/-12.8 beats/min, respectively; P < 0.05 for each) [7].
• Pretreatment with a mixed solution of PD 98059 and Y-27632 failed to cause further suppression of the urotensin II-induced pressor responses (4.5 +/-0.9 mmHg) [7].

Chemical compound and disease context of Uts2

• U-II was equally as efficacious as phenylephrine in inducing hypertrophy, measured by a reporter assay (EC(50) 0.7+/-0.2 nM) and [(3)H]-leucine incorporation (EC(50) 150+/-40 nM) [3].
• U-II shares similar biological activities with other hypertrophic G(q)-coupled receptor ligands such as angiotensin-II and endothelin-1, but a role for U-II in cardiomyocyte hypertrophy has not been characterized [3].
• Results: The ratio of heart weight/body weight, plasma lactate dehydrogenase activity, myocardial malondialdehyde and hydroxyproline concentration increased significantly in the ISO group, as well as UT mRNA expression, plasma and cardiac UII and ventricular Ang II, compared with the control group (P< 0.01) [8].
• Urotensin II accelerates cardiac fibrosis and hypertrophy of rats induced by isoproterenol [8].
• In vitro, 5 X10(-9 )-5 X10(-7 ) mol/L UII stimulated [3H]thymidine/[3H] proline incorporation into cardiac fibroblasts in a dose-dependent manner (P< 0.01).Conclusion: These results suggest that UII was involved in the development of cardiac fibrosis and hypertrophy by synergistic effects with ISO [8].

Biological context of Uts2

• Cloning, sequence analysis and tissue distribution of the mouse and rat urotensin II precursors [9].
• These results indicate that UII produces vasodilator and natriuretic effects in the kidney and that UII-induced vasodilation is associated with increased endothelial NO in the RA [10].
• In the present study, we have investigated the localization of UII receptor (GPR14) mRNA and UII binding sites in the rat CNS [11].
• Thus, UII is the first gene reported to show expression limited to the sacral pool of motoneurons, which are known to have particular properties in terms of targets and programmed cell death [12].
• These results indicate that circulating androgens are exerting a down-regulation of pro UII expression possibly by a direct action at the level of motoneurons [13].

Anatomical context of Uts2

• In situ hybridization histochemistry showed that the prepro-UII gene is predominantly expressed in motoneurons of the brainstem and spinal cord, suggesting that UII may play a role in the control of neuromuscular functions [9].
• Recent studies have postulated that the vasoactive peptide urotensin II (UII) plays a role in the control of vascular remodeling by inducing smooth muscle proliferation and fibroblast-mediated collagen deposition [14].
• In carotid arteries of uninjured rats (naïve group), there was weak expression of UII in endothelial cells and little to no expression in vascular smooth muscle cells [14].
• The present study examined the expression of UII mRNA and immunoreactivity in rat carotid arteries before and after balloon angioplasty [14].
• Urotensin II (UII) is a cyclic neuropeptide initially isolated from the caudal neurosecretory system of teleost fish [9].

Associations of Uts2 with chemical compounds

• This distribution suggests that the UII system is involved in functions regulated by acetylcholine, such as the sleep-wake cycle [6].
• Pre-treatment with pentolinium (5 mg/kg, i.v.) significantly attenuated the increases in mean arterial pressure (20 +/- 3 versus 8 +/- 2 mmHg, P <0.01) and heart rate (78 +/- 18 versus 7 +/- 5 beats/min, P <0.05) induced by ICV urotensin II [15].
• Human U-II was a potent vasoconstrictor of endothelium-intact isolated rat thoracic aorta (EC(50)=3.5+/-1.1 nM, R(max)=103+/-10% of control contraction induced by 60 mM KCl and 1 microM noradrenaline) [16].
• Moreover, human U-II caused concentration-dependent relaxation of 5-HT-precontracted arteries, which was abolished by L-NAME or removal of the endothelium [16].
• Human U-II contracted endothelium-intact rat isolated left anterior descending coronary arteries (EC(50)=1.3+/-0.8 nM, R(max)=20.1+/-4.9% of control contraction induced by 10 microM 5-HT) [16].

Regulatory relationships of Uts2

• Somatostatin inhibits active C1 secretion across the theophylline-treated rat colon but urotensin II, a dodecapeptide somatostatin analog from the teleost caudal neurosecretory system, is without effect [17].
• Urotensin II-induced activation of extracellular signal-regulated kinase in cultured vascular smooth muscle cells: involvement of cell adhesion-mediated integrin signaling [18].

Other interactions of Uts2

• Role of ERK and Rho kinase pathways in central pressor action of urotensin II [7].
• Urotensin-II increased Fos expression in the cingulate cortex and periaqueductal grey, suggesting important central roles for urotensin-II and its receptor [19].
• On the other hand, the cyclooxygenase inhibitor diclofenac significantly attenuated the urotensin II-induced coronary vasodilatation in both young and aged rats [20].
• Conversely, urotensin II stimulates active Na and C1 absorption across the posterior intestine of the 5% seawater-adapted goby, Gillichthys mirabilis, but somatostatin is ineffective [17].

Analytical, diagnostic and therapeutic context of Uts2

• The present study suggests an important role for UII in the pathogenesis of restenosis following balloon angioplasty [14].
• Moreover, whole-cell recordings from rat-brain slices show that UII selectively excites cholinergic PPT neurons via an inward current and membrane depolarization that were accompanied by membrane conductance decreases [6].
• UII mRNA was detected by reverse-transcription-polymerase chain reaction (RT-PCR) as early as E10 [12].
• Three weeks after castration, pro UII mRNA expression, as measured by semi-quantitative in situ hybridization, was increased by 17% and 58% in the ventral horn of the spinal cord and the facial nucleus, respectively [13].
• Pancreatic extracts were analyzed for UII by reversed-phase HPLC combined with a sensitive UII RIA [21].

References