International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, urotensin II-related peptide, and their receptor: from structure to function

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Hormone Antagonists / pharmacology
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Ligands
  • Molecular Sequence Data
  • Peptide Hormones / antagonists & inhibitors
  • Peptide Hormones / chemistry
  • Peptide Hormones / genetics
  • Peptide Hormones / metabolism*
  • Protein Conformation
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction
  • Structure-Activity Relationship
  • Urotensins / antagonists & inhibitors
  • Urotensins / chemistry
  • Urotensins / genetics
  • Urotensins / metabolism*


  • Hormone Antagonists
  • Intracellular Signaling Peptides and Proteins
  • Ligands
  • Peptide Hormones
  • Receptors, G-Protein-Coupled
  • UTS2B protein, human
  • UTS2R protein, human
  • Urotensins
  • urotensin II