370: Montelukast, a leukotriene receptor antagonist, inhibits spontaneous but not oxytocin-induced uterine contractions

Montelukast is a leukotriene receptor antagonist used to control asthma symptoms by inhibiting bronchiole smooth muscle contraction and by decreasing airway inflammation. Leukotrienes are known to increase uterine contractility and the uterus contains cysteinyl leukotriene receptor 1, the target for montelukast. Furthermore, recent work suggests that montelukast may decrease spontaneous uterine contractions, but its role in inhibiting oxytocin-induced contractions is not known. Using a murine model, we sought to determine if montelukast affects oxytocin-induced uterine contractions. Uterine horns were isolated from non-pregnant wildtype C57BL/6J female mice and suspended in a tissue organ bath that measures contraction force. The effect of montelukast on spontaneous and oxytocin-induced uterine contractility was measured. Dose response curves were constructed using nonlinear regression and the best fit curves compared between treatment groups and vehicle. Six mice were utilized for each treatment group. Montelukast significantly decreased spontaneous uterine contractility in a dose-dependent fashion to 49% of baseline compared to 63% of baseline in vehicle treated horns (p=0.045, Figure 1) at the highest tested dose (1 μM). In contrast, there was no difference in uterine contractility in response to oxytocin treatment (1nM to 100nM) among strips pre-treated with montelukast or vehicle control ([1 μM], 405% vs. 377% of baseline, p=0.59, Figure 2). Montelukast is a leukotriene receptor antagonist that decreases spontaneous uterine contractility but not oxytocin-induced uterine contractility in a murine model. As this agent also has anti-inflammatory properties, future work is needed to determine if montelukast can prolong pregnancy among women at high risk for preterm labor.