Autocrine activity of cysteinyl leukotrienes in human vascular endothelial cells: signaling through the cyslt2 receptor
Publication date: Available online 1 April 2015 Source:Prostaglandins & Other Lipid Mediators Author(s): Valérie Capra , Chiara Carnini , Maria Rosa Accomazzo , Antonio Di Gennaro , Marco Fiumicelli , Emanuele Borroni , Ivan Brivio , Carola Buccellati , Paolo Mangano , Silvia Carnevali , Gianenrico Rovati , Angelo Sala We evaluated the autocrine activities of cysteinyl leukotrienes (cysteinyl-LTs) in HUVEC and studied the signaling and the pharmacological profile of the CysLT2 receptor (CysLT2R) expressed by ECs, finally assessing the role of the CysLT2R in permeability alterations in a model of is...
Source: Prostaglandins and Other Lipid Mediators - April 1, 2015 Category: Lipidology Source Type: research
Acquired cisplatin resistance in human ovarian A2780 cancer cells correlates with shift in taurine homeostasis and ability to volume regulate
Cisplatin resistance is a major challenge in the treatment of cancer and develops through reduced drug accumulation and an increased ability to avoid drug-induced cell damage, cell shrinkage, and hence initiation of apoptosis. Uptake and release of the semiessential amino acid taurine contribute to cell volume homeostasis, and taurine has been reported to have antiapoptotic effects. Here we find that volume-sensitive taurine release in cisplatin-sensitive [wild-type (WT)] human ovarian cancer A2780 cells is reduced in the presence of the phospholipase A2 inhibitor bromenol lactone, the 5-lipoxygenase (5-LO) inhibitor ETH 6...
Source: AJP: Cell Physiology - December 15, 2014 Category: Cytology Authors: Sorensen, B. H., Thorsteinsdottir, U. A., Lambert, I. H. Tags: CALL FOR PAPERS Source Type: research
Structure based virtual screening of ligands to identify cysteinyl leukotriene receptor 1 antagonist.
Abstract
Montelukast and Zafirlukast are known leukotriene receptor antagonists prescribed in asthma treatment. However, these fall short as mono therapy and are frequently used in combination with inhaled glucocorticosteroids with or without long acting beta 2 agonists. Therefore, it is of interest to apply ligand and structure based virtual screening strategies to identify compounds akin to lead compounds Montelukast and Zafirlukast. Hence, compounds with structures having 95% similarity to these compounds were retrieved from NCBI׳s PubChem database. Compounds similar to lead were grouped and docked at ...
Source: Bioinformation - December 11, 2014 Category: Bioinformatics Authors: Bandaru S, Marri VK, Kasera P, Kovuri P, Girdhar A, Mittal DR, Ikram S, Gv R, Nayarisseri A Tags: Bioinformation Source Type: research
Cysteinyl leukotriene receptor-1 antagonists as modulators of innate immune cell function.
Authors: Theron AJ, Steel HC, Tintinger GR, Gravett CM, Anderson R, Feldman C
Abstract
Cysteinyl leukotrienes (cysLTs) are produced predominantly by cells of the innate immune system, especially basophils, eosinophils, mast cells, and monocytes/macrophages. Notwithstanding potent bronchoconstrictor activity, cysLTs are also proinflammatory consequent to their autocrine and paracrine interactions with G-protein-coupled receptors expressed not only on the aforementioned cell types, but also on Th2 lymphocytes, as well as structural cells, and to a lesser extent neutrophils and CD8(+) cells. Recognition of th...
Source: Journal of Immunology Research - November 19, 2014 Category: Allergy & Immunology Tags: J Immunol Res Source Type: research
Acquired Cisplatin Resistance in Humane Ovarian cancer A2780 cells correlates with shift in Taurine homeostasis and ability to volume regulate.
Abstract
Cisplatin resistance is a major challenge in the treatment of cancer and develops through reduced drug accumulation and an increased ability to avoid drug-induced cell damage, cell shrinkage and hence initiation of apoptosis. Uptake and release of the semi-essential amino acid taurine contribute to cell volume homeostasis and taurine has been reported to have anti-apoptotic effects. Here we find that volume sensitive taurine release in cisplatin sensitive (WT) humane ovarian cancer A2780 cells is reduced in the presence of the phospholipase A2 inhibitor bromoenol lacton, the 5-lipoxygenase (5-LO) ...
Source: Am J Physiol Cell Ph... - September 24, 2014 Category: Cytology Authors: Sørensen BH, Thorsteinsdottir UA, Lambert IH Tags: Am J Physiol Cell Physiol Source Type: research
Does zafirlukast reduce future risk of asthma exacerbations in adults? Systematic review and meta-analysis
Conclusions
Our study suggests that zafirlukast, as the first-line therapy, significantly reduces mild to moderate but not severe asthma exacerbations. In the add-on regimen, zafirlukast could not reduce asthma exacerbations, which would perhaps result from small sample size and needs to be further studied. (Source: Multidisciplinary Respiratory Medicine)
Source: Multidisciplinary Respiratory Medicine - May 28, 2014 Category: Respiratory Medicine Source Type: research
Pranlukast inhibits renal epithelial cyst progression via activation of AMP-activated protein kinase.
Abstract
Cysteinyl leukotriene receptor 1 (CysLT1) antagonists were found to inhibit chloride secretion in human airway epithelial cells. Since chloride secretion in renal epithelial cells, which shares common mechanisms with airway epithelial cells, plays important roles in renal cyst progression in polycystic kidney disease (PKD), this study was aimed to investigate effects of drugs acting as CysLT1 receptor antagonists on renal cyst progression and its underlying mechanisms. Effects of CystLT1 receptor antagonists on renal cyst growth and formation were determined using Madine Darby canine kidney (MDCK)...
Source: European Journal of Pharmacology - December 17, 2013 Category: Drugs & Pharmacology Authors: Pathomthongtaweechai N, Soodvilai S, Chatsudthipong V, Muanprasat C Tags: Eur J Pharmacol Source Type: research
Volume-sensitive release of organic osmolytes in the human lung epithelial cell line A549: role of the 5-lipoxygenase
We report that inhibition of the 5-lipoxygenase (5-LO) with AA861 or ETH 615-139, the cysteinyl leukotriene 1 receptor (CysLT1) with the antiasthmatic drug Zafirlukast, or the volume-sensitive organic anion channel (VSOAC) with DIDS blocks the release of organic osmolytes (taurine, meAIB) and the concomitant cell volume restoration following hypoosmotic swelling of human type II-like lung epithelial cells (A549). Reactive oxygen species (ROS) are produced in A549 cells upon hypotonic cell swelling by a diphenylene iodonium-sensitive NADPH oxidase. The swelling-induced taurine release is suppressed by ROS scavenging (butyla...
Source: AJP: Cell Physiology - July 1, 2013 Category: Cytology Authors: Holm, J. B., Grygorczyk, R., Lambert, I. H. Tags: ARTICLES Source Type: research
Assessment of absorption potential of poorly water-soluble drugs by using the dissolution/permeation system.
This study aims to assess the absorption potential of oral absorption of poorly water-soluble drugs by using the dissolution/permeation system (D/P system). The D/P system can be used to perform analysis of drug permeation under dissolution process and can predict the fraction of absorbed dose in humans. When celecoxib at 1/100 of a clinical dose was applied to the D/P system,% of dose dissolved and permeated significantly decreased with an increase in the applied amount, resulting in the oral absorption being predicted to be 22-55%. Whereas similar dissolution and permeation profiles of montelukast sodium was observed, es...
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 25, 2013 Category: Drugs & Pharmacology Authors: Kataoka M, Yano K, Hamatsu Y, Masaoka Y, Sakuma S, Yamashita S Tags: Eur J Pharm Biopharm Source Type: research
Cysteinyl leukotriene-receptor-1 antagonists interfere with PGE2 synthesis by inhibiting mPGES-1 activity.
Abstract
Because of their favourable safety profile and beneficial anti-inflammatory properties, the CysLT1 receptor antagonists (LTRA), montelukast, zafirlukast and pranlukast are approved for the treatment of asthma and are frequently prescribed as add-on therapeutics to reduce the amount of inhaled glucocorticoids and β2-agonists. There is evidence that some of these anti-inflammatory properties might be of a secondary nature and therefore, unrelated to the CysLT1 antagonism. Here, we show that LTRA inhibit PGE2 formation in cytokine- stimulated Hela and A549 carcinoma cells and in lipopolysaccharide (...
Source: Biochemical Pharmacology - May 14, 2013 Category: Drugs & Pharmacology Authors: Kahnt AS, Rörsch F, Diehl O, Hofmann B, Lehmann C, Steinbrink SD, Angioni C, Geisslinger G, Grösch S, Steinhilber D, Maier TJ Tags: Biochem Pharmacol Source Type: research
Volume-sensitive release of organic osmolytes in the human lung epithelial cell line A549 - Role of the 5-lipoxygenase.
We report that inhibition of the 5-lipoxygenase (5-LO) with AA861 or ETH 615-139, the cysteinyl leukotriene 1 receptor (CysLT1) with the anti-asthmatic drug Zafirlukast, or the volume-sensitive organic anion channel (VSOAC) with DIDS, blocks the release of organic osmolytes (taurine, meAIB) and the concomitant cell volume restoration following hypoosmotic swelling of human type II-like lung epithelial cells (A549). Reactive oxygen species (ROS) are produced in A549 cells upon hypotonic cell swelling by a diphenylene iodonium sensitive NADPH oxidase. The swelling-induced taurine release is suppressed by ROS scavenging (buty...
Source: American Journal of Physiology. Cell Physiology - March 13, 2013 Category: Cytology Authors: Holm JB, Grygorczyk R, Lambert IH Tags: Am J Physiol Cell Physiol Source Type: research
