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 mug/mL (+SE, 407.1 mug/mL; -SE, 207.84 mug/mL). Montelukast pretreatment significantly increased (P < .01) the PC15 NKA value (708.8 μg/mL; +SE, 890.47 μg/ml,; -SE, 564.15 μg/mL,) in comparison with placebo (394.4 μg/mL,; +SE, 491.88 μg/mL; -SE, 248.16 μg/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 μg/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 anti-inflammatory effects of LT antagonists
Inhibitory effect of a leukotriene receptor antagonist (montelukast) on neurokinin A-induced bronchoconstriction
CRIMI, Nunzio;PALERMO, Filippo;VANCHERI, CARLO
2003-01-01
Abstract
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 mug/mL (+SE, 407.1 mug/mL; -SE, 207.84 mug/mL). Montelukast pretreatment significantly increased (P < .01) the PC15 NKA value (708.8 μg/mL; +SE, 890.47 μg/ml,; -SE, 564.15 μg/mL,) in comparison with placebo (394.4 μg/mL,; +SE, 491.88 μg/mL; -SE, 248.16 μg/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 μg/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 anti-inflammatory effects of LT antagonistsFile | Dimensione | Formato | |
---|---|---|---|
effect of a leukotriene receptor.pdf
solo gestori archivio
Tipologia:
Versione Editoriale (PDF)
Dimensione
190.65 kB
Formato
Adobe PDF
|
190.65 kB | Adobe PDF | Visualizza/Apri |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.