1. Leukotriene receptor antagonist as a novel tocolytic in an in vitro model of human uterine contractility.
- Author
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Corriveau S, Rousseau É, Blouin S, and Pasquier JC
- Subjects
- Adult, Area Under Curve, Calcium pharmacology, Cyclopropanes, Extraembryonic Membranes chemistry, Female, Humans, Inhibitory Concentration 50, Leukotriene D4 pharmacology, Myometrium chemistry, Nifedipine pharmacology, Placenta chemistry, Pregnancy, Sulfides, Tissue Culture Techniques, Tocolytic Agents pharmacology, Young Adult, Acetates pharmacology, Leukotriene Antagonists pharmacology, Muscle Contraction drug effects, Myometrium drug effects, Quinolines pharmacology, Receptors, Leukotriene analysis
- Abstract
Objective: This study analyzed the ability of montelukast, a cysteinyl-leukotrienes receptor antagonist and anti-inflammatory agent, to produce a consistent tocolytic effect alone or in combination with nifedipine, a calcium (Ca(2+)) channel blocker currently used in clinical practice., Study Design: Uterine biopsies were obtained from consenting women undergoing elective cesarean sections at term (n=20). Myometrial microsomal fractions were analyzed by immunoblotting to quantify relative cysteinyl leukotrienes receptor 1 (CysLTR1) levels. Isometric tension measurements were performed in vitro on human myometrial strips (n=120) in isolated organ baths in order to establish concentration-response curves to montelukast and to quantify changes in Ca(2+) sensitivity on β-escin permeabilized tissues., Results: Immunodetection analysis revealed the presence of CysLTR1 receptor in uterine tissues, fetal membranes and placenta. A significant increase in area under the curve (AUC) was quantified following the addition of leukotriene D4 (LTD4) (0.01-0.3 μM), an end-product of the lipoxygenase pathway. Conversely, addition of montelukast produced a significant tocolytic effect by decreasing the frequency and AUC (IC₅₀=1 μM). Moreover, addition of montelukast also resulted in a reduced Ca(2+) sensitivity as compared to control tissues (EC₅₀ values of 654 and 403 nM; p=0.02 at pCa 6), while an additive effect was observed in combination with 0.1 nM nifedipine (p=0.004)., Conclusion: This original study demonstrates the potency of montelukast as a tocolytic agent in an in vitro human uterine model. Montelukast, in combination with nifedipine, could represent a therapeutic approach to reduce inflammation associated with prematurity while facilitating the inhibition of preterm labor., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2014
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