RT Journal Article
SR Electronic
T1 International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, Urotensin II–Related Peptide, and Their Receptor: From Structure to Function
JF Pharmacological Reviews
JO Pharmacol Rev
FD American Society for Pharmacology and Experimental Therapeutics
SP 214
OP 258
DO 10.1124/pr.114.009480
VO 67
IS 1
A1 Vaudry, Hubert
A1 Leprince, Jérôme
A1 Chatenet, David
A1 Fournier, Alain
A1 Lambert, David G.
A1 Le Mével, Jean-Claude
A1 Ohlstein, Eliot H.
A1 Schwertani, Adel
A1 Tostivint, Hervé
A1 Vaudry, David
A2 R. Sibley, David
YR 2015
UL http://pharmrev.aspetjournals.org/content/67/1/214.abstract
AB 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.