This article is part of the Research Topic Neuropeptide GPCRs in neuroendocrinology

Review ARTICLE

Front. Endocrinol., 02 January 2013 | http://dx.doi.org/10.3389/fendo.2012.00174

Update on the urotensinergic system: new trends in receptor localization, activation, and drug design

  • 1Laboratoire d'études moléculaires et pharmacologiques des peptides, INRS – Institut Armand-Frappier, Université du Québec, Ville de Laval, QC, Canada
  • 2Laboratoire International Associé Samuel de Champlain (INSERM/INRS-Université de Rouen), France

The urotensinergic system plays central roles in the physiological regulation of major mammalian organ systems, including the cardiovascular system. As a matter of fact, this system has been linked to numerous pathophysiological states including atherosclerosis, heart failure, hypertension, diabetes as well as psychological, and neurological disorders. The delineation of the (patho)physiological roles of the urotensinergic system has been hampered by the absence of potent and selective antagonists for the urotensin II-receptor (UT). Thus, a more precise definition of the molecular functioning of the urotensinergic system, in normal conditions as well as in a pathological state is still critically needed. The recent discovery of nuclear UT within cardiomyocytes has highlighted the cellular complexity of this system and suggested that UT-associated biological responses are not only initiated at the cell surface but may result from the integration of extracellular and intracellular signaling pathways. Thus, such nuclear-localized receptors, regulating distinct signaling pathways, may represent new therapeutic targets. With the recent observation that urotensin II (UII) and urotensin II-related peptide (URP) exert different biological effects and the postulate that they could also have distinct pathophysiological roles in hypertension, it appears crucial to reassess the recognition process involving UII and URP with UT, and to push forward the development of new analogs of the UT system aimed at discriminating UII- and URP-mediated biological activities. The recent development of such compounds, i.e. urocontrin A and rUII(1–7), is certainly useful to decipher the specific roles of UII and URP in vitro and in vivo. Altogether, these studies, which provide important information regarding the pharmacology of the urotensinergic system and the conformational requirements for binding and activation, will ultimately lead to the development of potent and selective drugs.

Keywords: urotensin II, urotensin II-related peptide, allosteric modulation, biased agonist, nuclear receptors

Citation: Chatenet D, Nguyen T-TM, Létourneau M and Fournier A (2013) Update on the urotensinergic system: new trends in receptor localization, activation, and drug design. Front. Endocrin. 3:174. doi: 10.3389/fendo.2012.00174

Received: 26 September 2012; Paper pending published: 30 October 2012;
Accepted: 10 December 2012; Published online: 02 January 2013.

Edited by:

Hubert Vaudry, University of Rouen, France

Reviewed by:

Stacia A. Sower, University of New Hampshire, USA
Ishwar S. Parhar, Monash University, Malaysia

Copyright © 2013 Chatenet, Nguyen, Létourneau and Fournier. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

*Correspondence: David Chatenet and Alain Fournier, Laboratoire d'études moléculaires et pharmacologiques des peptides, INRS – Institut Armand-Frappier, Université du Québec, 531 Boulevard des Prairies, Ville de Laval, QC H7V 1B7, Canada. e-mail: david.chatenet@iaf.inrs.ca; alain.fournier@iaf.inrs.ca