Bladder Endothelin-1 Receptor Binding of Bosentan and Ambrisentan

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Endothelin-1 receptors in rat tissues: characterization by bosentan, ambrisentan and CI-1020.

The present study aimed to characterize comparatively endothelin-1 (ET-1) receptors in rat tissues by radioligand binding assay using [(125)I]ET-1 and to examine receptor binding after oral administration of bosentan. Significant amount of specific [(125)I]ET-1 binding was detected in the lung, heart, kidney, bladder and cerebral cortex of rats. ET-1, bosentan, ambrisentan, and CI-1020 inhibite...

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Slow Receptor Dissociation Kinetics Differentiate Macitentan from Other Endothelin Receptor Antagonists in Pulmonary Arterial Smooth Muscle Cells

Two endothelin receptor antagonists (ERAs), bosentan and ambrisentan, are currently approved for the treatment of pulmonary arterial hypertension (PAH), a devastating disease involving an activated endothelin system and aberrant contraction and proliferation of pulmonary arterial smooth muscle cells (PASMC). The novel ERA macitentan has recently concluded testing in a Phase III morbidity/mortal...

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Upregulation of Endothelin-1/Endothelin A Receptor Expression Correlates with Heparanase Expression in Ovarian Carcinoma

Background: Heparanase and endothelin-1/endothelin A receptor (ET-1/ETAR) expressions increase in cancer. This condition enhances tumor progression and correlates with poor survival. Limited data are documented regarding the role of heparanase and ET-1/ETAR in epithelial ovarian cancer (EOC). We sought to characterize the correlation between heparanase and ET-1/ETAR in EOC.Methods: Thirty patie...

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Developmental changes in Endothelin-1 and Endothelin type A receptor expression in the lungs of chickens (Broiler versus layer)

Background: Broilers lung mechanisms that regulate endothelin (ET) in the lung are complex and poorly understood. Objectives: Methods: In this experiment lung ET-1 mRNA levels and lung mRNA expression for the ET(A) receptors were determined in lung tissue weekly (term = 42 days, intervals = 7 days). Serum endothelin concentration was also measured at these ages. Results: The study showed that e...

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Distinct ETA Receptor Binding Mode of Macitentan As Determined by Site Directed Mutagenesis

The competitive endothelin receptor antagonists (ERA) bosentan and ambrisentan, which have long been approved for the treatment of pulmonary arterial hypertension, are characterized by very short (1 min) occupancy half-lives at the ET(A) receptor. The novel ERA macitentan, displays a 20-fold increased receptor occupancy half-life, causing insurmountable antagonism of ET-1-induced signaling in p...

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ژورنال

عنوان ژورنال: Journal of Pharmacological Sciences

سال: 2014

ISSN: 1347-8613,1347-8648

DOI: 10.1254/jphs.13198fp