Urotensin Receptor

Urotensin II (U-II) was first isolated from the fish spinal cord and has been recognized as a hormone in the neurosecretory system of teleost fish for over 40 years. U-II is the most potent vasoconstrictor known and is even more potent than endothelin-1 (ET-1). U-II is a cyclic peptide and shares a similar sequence with somatostatin. U-II isoforms from human, monkey, pig, rat, mouse and goby all contain a conserved C-terminal cyclic hexapeptide sequence (Cys-Phe-Trp-Lys-Tyr-Cys) that confers most of the biological activity. The N-terminus of U-II differs in length and sequence depending on the animal species. The receptor for hU-II turned out to be the orphan G-protein-coupled receptor 14 (GPR14). The UT receptor is found in human brain, spinal cord, leukocytes, ventricular myocardium, vascular endothelial and smooth muscle cells, kidney cortex, adrenal gland, pituitary and thyroid, with the highest density in skeletal muscle and cerebral cortex. 
The UT receptor is coupled to the Gαq/11 signal transduction pathway, the activation of which leads to an increase in inositol triphosphate and mobilization of intracellular Ca2+. It involves small GTPase RhoA and its downstream effector Rho-kinase, phospholipase C, protein kinase C and tyrosine kinase, PKC-independent phosphylation of myosin light chain(MLC-2) as well as the Ca2+-calmodulin/MLC kinase system, extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase. Rho signalling pathway and ERK may also be involved in U-II-induced vascular smooth muscle cell proliferation.


1.Ong KL,et al. Cardiovasc Drugs Ther. 2005;19(1):65–75.