Effects of Urotensin II Receptor Antagonist, GSK1440115, in Asthma

Effects of Urotensin II Receptor Antagonist, GSK1440115, in Asthma

BACKGROUND Urotensin II (U-II) is highly expressed in the human lung and has been implicated in regulating respiratory physiology in preclinical studies. Our objective was to test antagonism of the urotensin (UT) receptor by GSK1440115, a novel, competitive, and selective inhibitor of the UT receptor, as a therapeutic strategy for the treatment of asthma. METHODS Safety, tolerability, and pha...

Inhibitory Effect of an Urotensin II Receptor Antagonist on Proinflammatory Activation Induced by Urotensin II in Human Vascular Endothelial Cells

In this study, we investigated the effects of a selective urotensin II (UII) receptor antagonist, SB-657510, on the inflammatory response induced by UII in human umbilical vein endothelial cells (EA.hy926) and human monocytes (U937). UII induced inflammatory activation of endothelial cells through expression of proinflammatory cytokines (IL-1β and IL-6), adhesion molecules (VCAM-1), and tissue ...

Pharmacology of the Urotensin-II Receptor Antagonist ACT-058362: First Demonstration of a Pathophysiological Role of the Urotensin System

The urotensin-II receptor antagonist palosuran improves pancreatic and renal function in diabetic rats.

Urotensin-II (U-II) is a cyclic peptide that acts through a specific G-protein-coupled receptor, UT receptor. Urotensin-II and UT receptors have been described in pancreas and kidney, but their function is not well understood. We studied the effects of chronic treatment of diabetic rats with the orally active selective U-II receptor antagonist palosuran. Streptozotocin treatment causes pancreat...

Urotensin II receptor antagonist attenuates monocrotaline-induced cardiac hypertrophy in rats.

Urotensin II (UII) is a vasoactive peptide with potent cardiovascular effects through a G protein-coupled receptor. Hypoxia stimulates the secretion of UII and atrial natriuretic peptide (ANP). However, the effect of UII on hypoxia-induced cardiac hypertrophy is still controversial. The present study was conducted to determine whether human UII (hUII)-mediated ANP secretion influences hypoxia-i...