Inhibitory effect of a leukotriene

Background: Tachykinins are potent contractors of human airways producing a dose-related bronchoconstriction when administered by means of inhalation to asthmatic subjects. Objective: The aim of this study was to examine the effective role played by leukotrienes (LTs) in neurokinin A (NKA)-induced bronchoconstriction in asthmatic patients. Methods: To address this question, we investigated the protective effect of a selective cysteinyl LT receptor antagonist, montelukast, against inhaled NKA and determined LTE4 excretion in the urine. Results: Inhaled NKA in the absence of any drug treatment produced a concentration-related bronchospasm with a geometric mean provocative concentration required to produce a 15% decrease in FEV1 from the postsaline baseline value (PC15) value of 290.9 ?g/mL (+SE, 407.1 ?g/mL; -SE, 207.84 ?g/mL). Montelukast pretreatment significantly increased (P < .01) the PC15 NKA value (708.8 ?g/mL; +SE, 890.47 ?g/mL; -SE, 564.15 ?g/mL) in comparison with placebo (394.4 ?g/mL; +SE, 491.88 ?g/mL; -SE, 248.16 ?g/mL) and produced a shift of the NKA concentration-response curve to the right in all the subjects studied. When compared with placebo, montelukast did not have a significant protective effect against methacholine challenge; the geometric mean PC15 values obtained were 0.87 and 0.96 mg/mL with placebo and montelukast, respectively. Although we have not observed any increase in urinary LTE4 excretion after NKA inhalation, we have shown that pretreatment of asthmatic subjects with montelukast elicits a significant protection against NKA-induced bronchoconstriction. Conclusion: In asthmatic subjects NKA-induced bronchoconstriction is indirectly caused by the release of LTs, and this mechanism could explain some of the antiasthmatic and antiinflammatory effects of LT antagonists.