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Leukotriene receptor antagonist as a novel tocolytic in an in vitro model of human uterine contractility.

Eur J Obstet Gynecol Reprod Biol. 2014 Jun;177:77-83. doi: 10.1016/j.ejogrb.2014.02.042. Epub 2014 Mar 12.

Corriveau S1, Rousseau E2, Blouin S3, Pasquier JC4.
1Obstetrics and Gynecology, CHUS, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada; Physiology and Biophysics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada.2Physiology and Biophysics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada.3Obstetrics and Gynecology, CHUS, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada.4Obstetrics and Gynecology, CHUS, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada. Electronic address: Jean-Charles.Pasquier@usherbrooke.ca.
Eur J Obstet Gynecol Reprod Biol
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 ß-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) (0.01-0.3µM), an end-product of the lipoxygenase pathway. Conversely, addition of montelukast produced a significant tocolytic effect by decreasing the frequency and AUC (IC50=1µM). Moreover, addition of montelukast also resulted in a reduced Ca(2+) sensitivity as compared to control tissues (EC50 values of 654 and 403nM; p=0.02 at pCa 6), while an additive effect was observed in combination with 0.1nM 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.
Full Text Source: Elsevier Science
PMID:24735655 | http://www.ncbi.nlm.nih.gov/pubmed/24735655

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