Institut National de la Santé et de la Recherche Médicale, U982, Institute for Research and Innovation in Biomedicine, Mont-Saint-Aignan, France (H.V., J.L., D.V.), University of Rouen, Mont-Saint-Aignan, France (H.V., J.L., D.V.); Institut National de la Recherche Scientifique-Institut Armand Frappier, Laval, Québec, Canada (D.C., A.F.); International Associated Laboratory Samuel de Champlain, University of Rouen, Mont-Saint-Aignan, France (H.V., J.L., D.C., A.F., D.V.); Department of Cardiovascular Sciences, Division of Anaesthesia, Critical Care and Pain Management, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester, United Kingdom (D.G.L.); Institut National de la Santé et de la Recherche Médicale, U1101, Laboratoire de Traitement de l'Information Médicale, Laboratoire de Neurophysiologie, Université Européenne de Bretagne, Brest, France (J.-C.L.M.); AltheRx Pharmaceuticals, Malvern, Pennsylvania (E.H.O.); Division of Cardiology, Montreal General Hospital, McGill University Health Center, Montreal, Québec, Canada (A.S.); and Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7221, Evolution des Régulations Endocriniennes, Muséum National d'Histoire Naturelle, Paris, France (H.T.)
Institut National de la Santé et de la Recherche Médicale, U982, Institute for Research and Innovation in Biomedicine, Mont-Saint-Aignan, France (H.V., J.L., D.V.), University of Rouen, Mont-Saint-Aignan, France (H.V., J.L., D.V.); Institut National de la Recherche Scientifique-Institut Armand Frappier, Laval, Québec, Canada (D.C., A.F.); International Associated Laboratory Samuel de Champlain, University of Rouen, Mont-Saint-Aignan, France (H.V., J.L., D.C., A.F., D.V.); Department of Cardiovascular Sciences, Division of Anaesthesia, Critical Care and Pain Management, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester, United Kingdom (D.G.L.); Institut National de la Santé et de la Recherche Médicale, U1101, Laboratoire de Traitement de l'Information Médicale, Laboratoire de Neurophysiologie, Université Européenne de Bretagne, Brest, France (J.-C.L.M.); AltheRx Pharmaceuticals, Malvern, Pennsylvania (E.H.O.); Division of Cardiology, Montreal General Hospital, McGill University Health Center, Montreal, Québec, Canada (A.S.); and Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7221, Evolution des Régulations Endocriniennes, Muséum National d'Histoire Naturelle, Paris, France (H.T.).
Pharmacol Rev. 2015;67(1):214-58. doi: 10.1124/pr.114.009480.
Urotensin II (UII) is a cyclic neuropeptide that was first isolated from the urophysis of teleost fish on the basis of its ability to contract the hindgut. Subsequently, UII was characterized in tetrapods including humans. Phylogenetic studies and synteny analysis indicate that UII and its paralogous peptide urotensin II-related peptide (URP) belong to the somatostatin/cortistatin superfamily. In mammals, the UII and URP genes are primarily expressed in cholinergic neurons of the brainstem and spinal cord. UII and URP mRNAs are also present in various organs notably in the cardiovascular, renal, and endocrine systems. UII and URP activate a common G protein-coupled receptor, called UT, that exhibits relatively high sequence identity with somatostatin, opioid, and galanin receptors. The UT gene is widely expressed in the central nervous system (CNS) and in peripheral tissues including the retina, heart, vascular bed, lung, kidney, adrenal medulla, and skeletal muscle. Structure-activity relationship studies and NMR conformational analysis have led to the rational design of a number of peptidic and nonpeptidic UT agonists and antagonists. Consistent with the wide distribution of UT, UII has now been shown to exert a large array of biologic activities, in particular in the CNS, the cardiovascular system, and the kidney. Here, we review the current knowledge concerning the pleiotropic actions of UII and discusses the possible use of antagonists for future therapeutic applications.
尿鸟苷素 II（UII）是一种环状神经肽，最初是根据其收缩后肠的能力从硬骨鱼的脑下垂体中分离出来的。随后，在包括人类在内的四足动物中对 UII 进行了特征描述。系统发育研究和基因同线性分析表明，UII 和其同源肽尿鸟苷素 II 相关肽（URP）属于生长抑素/促皮质素家族。在哺乳动物中，UII 和 URP 基因主要在脑干和脊髓的胆碱能神经元中表达。UII 和 URP mRNA 也存在于各种器官中，特别是心血管、肾脏和内分泌系统。UII 和 URP 激活一种共同的 G 蛋白偶联受体，称为 UT，其与生长抑素、阿片类和甘丙肽受体具有相对较高的序列同一性。UT 基因广泛表达于中枢神经系统（CNS）和外周组织中，包括视网膜、心脏、血管床、肺、肾脏、肾上腺髓质和骨骼肌。结构-活性关系研究和 NMR 构象分析导致了许多肽类和非肽类 UT 激动剂和拮抗剂的合理设计。与 UT 的广泛分布一致，UII 现已被证明具有多种生物学活性，特别是在中枢神经系统、心血管系统和肾脏中。在这里，我们回顾了关于 UII 的多效性作用的现有知识，并讨论了使用拮抗剂进行未来治疗应用的可能性。
