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Bladder Smooth Muscle Strip Contractility as a Method to Evaluate Lower Urinary Tract Pharmacology
Published on: August 18, 2014
International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, urotensin II-related peptide, and their
Hubert Vaudry1, Jérôme Leprince2, David Chatenet2
1Institut 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.) hubert.vaudry@univ-rouen.fr.
Abstract:
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.
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