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Drug Discov Today ; 24(11): 2170-2180, 2019 11.
Article in English | MEDLINE | ID: mdl-31430542

ABSTRACT

Urotensin II (UII) is a vasoactive peptide that interacts with a specific receptor called the UT receptor. UII has been implicated in cardiovascular regulation, with promising therapeutic applications based on UT receptor antagonism. The endogenous ligands of the UT receptor: UII and urotensin-related peptide (URP), differentially bind and activate this receptor. Also, the receptor localization is not restricted to the plasma membrane, possibly inducing different physiological responses that could support its inconsistent, but potent, vasoactive activity. These properties could explain the disappointing outcomes in clinical studies, in contrast to the positive preclinical results regarding heart failure, pulmonary hypertension, atherosclerosis and diabetes mellitus. These aspects should be considered in future investigations to a better comprehension of the role of UII as a potential therapeutic target.


Subject(s)
Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/metabolism , Drug Discovery/methods , Receptors, G-Protein-Coupled/antagonists & inhibitors , Urotensins/antagonists & inhibitors , Animals , Cardiovascular Agents/chemistry , Cardiovascular Agents/pharmacology , Disease Models, Animal , Humans , Ligands , Receptors, G-Protein-Coupled/genetics , Signal Transduction , Tissue Distribution , Urotensins/biosynthesis
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