Urotensin II (114-124), human TFA is an 11-amino-acid peptide that stimulates its obligatory G protein-coupled urotensin II receptors (UT), by binding to the orphan G-protein-coupled receptor 14 (GPR14) to modulate cardiovascular function in humans[1-2].
In vitro, Urotensin II (114-124), human TFA at concentrations ranging from 10-13-10-7M has been used to treat arteries. Vasoconstrictive effects of Urotensin II (114-124), human TFA have been observed in isolated human coronary arteries (responders' data: −log[EC50] 10.05±0.46, Emax 15.39±6.53% of 100mM KCl contraction), mammary arteries (responders' data: −log[EC50] 9.71±0.90, Emax 16.41±6.15% of 100mM KCl contraction), and radial arteries (responders' data: −log[EC50] 9.52±0.83, Emax 19.65±6.26% of 100mM KCl contraction)[3]. Urotensin II (114-124), human TFA (1pM–0.1μM) has been shown to induce vasodilation in very small human pulmonary arteries[4]. Urotensin II (114-124), human TFA (10−7mol/L) stimulation of neonatal cardiac fibroblasts increased the level of mRNA transcripts for procollagens α1(I), α1(III), and fibronectin by 139±15% (P<0.01), 59±5% (P<0.05), and 141±14% (P<0.01), respectively, with a concomitant 23±2% increase in collagen peptide synthesis[5].
In vivo, Urotensin II (114-124), human TFA markedly increases total peripheral resistance in anaesthetized cynomolgus monkeys in a dose-dependent manner, a response associated with profound cardiac contractile dysfunction[6]. A biphasic cardiovascular response to bolus i.v. injection of human Urotensin II (114-124), human TFA (3nmol/kg) in conscious, male, Sprague-Dawley (SD) rats was identified, characterized by initial (0-5min) tachycardia, hypotension, and vasodilatation of the mesenteric and hindquarters arteries, followed by later (30-120min) tachycardia, hindquarters vasodilatation, and a modest rise in blood pressure[7].
References:
[1] Zhu YC, Zhu YZ, Moore PK. The role of urotensin II in cardiovascular and renal physiology and diseases. Br J Pharmacol. 2006;148(7):884-901.
[2] Russell FD. Urotensin II in cardiovascular regulation. Vasc Health Risk Manag. 2008;4(4):775-785.
[3] Maguire JJ, Kuc RE, Davenport AP. Orphan-receptor ligand human urotensin II: receptor localization in human tissues and comparison of vasoconstrictor responses with endothelin-1. Br J Pharmacol. 2000;131(3):441-446.
[4] Stirrat A, Gallagher M, Douglas SA, et al. Potent vasodilator responses to human urotensin-II in human pulmonary and abdominal resistance arteries. Am J Physiol Heart Circ Physiol. 2001;280(2):H925-H928.
[5] Tzanidis A, Hannan RD, Thomas WG, et al. Direct actions of urotensin II on the heart: implications for cardiac fibrosis and hypertrophy. Circ Res. 2003;93(3):246-253.
[6] Ames RS, Sarau HM, Chambers JK, et al. Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14. Nature. 1999;401(6750):282-286.
[7] Gardiner SM, March JE, Kemp PA, Bennett T. Bolus injection of human UII in conscious rats evokes a biphasic haemodynamic response. Br J Pharmacol. 2004;143(3):422-430.
Urotensin II (114-124), human TFA 是一种含有11个氨基酸的肽，能够通过结合孤儿G蛋白偶联受体14（GPR14）激活其必需的G蛋白偶联尿激肽II受体（UT），从而调节人类的心血管功能[1-2]。
在体外，Urotensin II (114-124), human TFA 以10-13-10-7M的浓度范围用于处理动脉。在分离的人类冠状动脉（反应者数据：−log[EC₅₀] 10.05±0.46，最大效应为100mM KCl收缩的15.39±6.53%）、乳腺动脉（反应者数据：−log[EC₅₀] 9.71±0.90，最大效应为100mM KCl收缩的16.41±6.15%）和桡动脉（反应者数据：−log[EC₅₀] 9.52±0.83，最大效应为100mM KCl收缩的19.65±6.26%）中观察到Urotensin II (114-124), human TFA 的血管收缩效应[3]。在非常小的人类肺动脉中，Urotensin II (114-124), human TFA（1pM–0.1μM）被证明可以引起血管舒张[4]。Urotensin II (114-124), human TFA（10⁻⁷mol/L）刺激新生心肌成纤维细胞，使前胶原蛋白α1(I)、α1(III)和纤维连接蛋白的mRNA转录水平分别增加了139±15%（P<0.01）、59±5%（P<0.05）和141±14%（P<0.01），同时胶原蛋白肽合成增加了23±2%[5]。
在体内，Urotensin II (114-124), human TFA（10–3000pmol/kg）以剂量依赖的方式显著增加了的食蟹猴的总外周阻力，这种反应与严重的心脏收缩功能障碍有关[6]。在清醒的雄性Sprague-Dawley（SD）大鼠中，通过静脉注射Urotensin II (114-124), human TFA（3nmol/kg）发现了双相心血管反应，其特征为初始阶段（0-5分钟）出现心动过速、低血压以及肠系膜和后肢动脉的血管扩张，随后在后期（30-120分钟）出现心动过速、后肢动脉扩张以及轻微的血压升高[7]。