ArticleBritish journal of pharmacology2006
The peptidic urotensin-II receptor ligand GSK248451 possesses less intrinsic activity than the low-efficacy partial agonists SB-710411 and urantide in native mammalian tissues and recombinant cell systems.
Article in British journal of pharmacology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 36 citations in OpenAlex.
- The urotensin II receptor triggers an early meningeal response and a delayed macrophage-dependent vasospasm after subarachnoid hemorrhage in male mice.Nature communications · 2024Article
- Effects of urotensin II and its specific receptor antagonist urantide on rat vascular smooth muscle cells.Bosnian journal of basic medical sciences · 2013Article
- Discovery of new antagonists aimed at discriminating UII and URP-mediated biological activities: insight into UII and URP receptor activation.British journal of pharmacology · 2013Article
- Urotensin-II Ligands: An Overview from Peptide to Nonpeptide Structures.Journal of amino acids · 2013Article
- In vitro siRNA-mediated knockdown of the UT receptor: implications of density on the efficacy of a range of UT ligands.Naunyn-Schmiedeberg's archives of pharmacology · 2012Article
- GSK1562590, a slowly dissociating urotensin-II receptor antagonist, exhibits prolonged pharmacodynamic activity ex vivo.British journal of pharmacology · 2010Article
- A rat brain atlas of urotensin-II receptor expression and a review of central urotensin-II effects.Naunyn-Schmiedeberg's archives of pharmacology · 2010Review
- Direct inotropic effects of exogenous and endogenous urotensin-II: divergent actions in failing and nonfailing human myocardium.Circulation. Heart failure · 2009Article
- Palosuran inhibits binding to primate UT receptors in cell membranes but demonstrates differential activity in intact cells and vascular tissues.British journal of pharmacology · 2008Article
- Role of urotensin II and its receptor in health and disease.Journal of anesthesia · 2007Review
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15 authors at 3 institutions in 3 countries.
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Abstract
Several peptidic urotensin-II (UT) receptor antagonists exert 'paradoxical' agonist activity in recombinant cell- and tissue-based bioassay systems, likely the result of differential urotensin-II receptor (UT receptor) signal transduction/coupling efficiency between assays. The present study has examined this phenomenon in mammalian arteries and recombinant UT-HEK (human embryonic kidney) cells.BacMam-mediated recombinant UT receptor upregulation in HEK cells augmented agonist activity for all four peptidic UT ligands studied. The nominal rank order of relative intrinsic efficacy was U-II>urantide ([Pen(5)-DTrp(7)-Orn(8)]hU-II(4-11))>SB-710411 (Cpa-c[DCys-Pal-DTrp-Lys-Val-Cys]-Cpa-amide)>>GSK248451 (Cin-c[DCys-Pal-DTrp-Orn-Val-Cys]-His-amide) (the relative coupling efficiency of recombinant HEK cells was cat>human>>rat UT receptor). The present study further demonstrated that the use of high signal transduction/coupling efficiency isolated blood vessel assays (primate>cat arteries) is required in order to characterize UT receptor antagonism thoroughly. This cannot be attained simply by using the rat isolated aorta, an artery with low signal transduction/coupling efficiency in which low-efficacy agonists appear to function as antagonists. In contrast to the 'low-efficacy agonists' urantide and SB-710411, GSK248451 functioned as a potent UT receptor antagonist in all native isolated tissues studied (UT receptor selectivity was confirmed in the rat aorta). Further, GSK248451 exhibited an extremely low level of relative intrinsic activity in recombinant HEK cells (4-5-fold less than seen with urantide). Since GSK248451 (1 mg kg(-1), i.v.) blocked the systemic pressor actions of exogenous U-II in the anaesthetized cat, it represents a suitable peptidic tool antagonist for delineating the role of U-II in the aetiology of mammalian cardiometabolic diseases.
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