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Role of cysteinyl leukotrienes in adenosine 5'-monophosphate induced bronchoconstriction in asthma.
Thorax. 2002 Apr; 57(4):323-7.T

Abstract

BACKGROUND

Adenosine induced bronchoconstriction in patients with asthma is thought to be mediated by the synthesis and release of autacoids from airway mast cells. In vitro, adenosine induced constriction of asthmatic bronchi is blocked by a combination of specific histamine and cysteinyl leukotriene receptor antagonists, but the relative contribution of these mediators in vivo is unclear. We hypothesised that adenosine induced bronchoconstriction in asthmatic patients may be blocked by pretreatment with the orally active selective cysteinyl leukotriene-1 (CysLT(1)) receptor antagonist, montelukast.

METHODS

In a randomised, double blind, crossover study, oral montelukast (10 mg) or placebo was administered once daily on two consecutive days to 18 patients with mild to moderate persistent atopic asthma. Incremental doses of adenosine 5'-monophosphate (AMP) from 0.39 to 400 mg/ml were inhaled by dosimeter and the dose producing a 20% fall in FEV(1) (PC(20)AMP) after AMP inhalation was recorded. Leukotriene E(4) (LTE(4)) urinary concentrations were measured by enzyme immunoassay 4 hours after AMP challenge.

RESULTS

Montelukast pretreatment provided highly significant protection against adenosine induced bronchoconstriction, with geometric mean PC(20)AMP values of 52.6 mg/ml (95% CI 35.2 to 78.7) after placebo and 123.9 mg/ml (95% CI 83.0 to 185.0) after montelukast (p=0.006). The geometric mean of the montelukast/placebo PC(20)AMP ratio was 2.4 (95% CI 1.3 to 4.2). Montelukast had no significant effect on 4 hour urinary excretion of LTE(4) compared with placebo.

CONCLUSIONS

Selective CysLT(1) receptor antagonism with montelukast provides highly significant protection against AMP induced bronchoconstriction in patients with atopic asthma, implying that cysteinyl leukotrienes are generated from airway mast cells through preferential activation of their A(2B) receptors.

Authors+Show Affiliations

Division of Respiratory Cell and Molecular Biology, University of Southampton School of Medicine, Southampton General Hospital, Southampton SO16 6YD, UK. s.rorke@soton.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11923550

Citation

Rorke, S, et al. "Role of Cysteinyl Leukotrienes in Adenosine 5'-monophosphate Induced Bronchoconstriction in Asthma." Thorax, vol. 57, no. 4, 2002, pp. 323-7.
Rorke S, Jennison S, Jeffs JA, et al. Role of cysteinyl leukotrienes in adenosine 5'-monophosphate induced bronchoconstriction in asthma. Thorax. 2002;57(4):323-7.
Rorke, S., Jennison, S., Jeffs, J. A., Sampson, A. P., Arshad, H., & Holgate, S. T. (2002). Role of cysteinyl leukotrienes in adenosine 5'-monophosphate induced bronchoconstriction in asthma. Thorax, 57(4), 323-7.
Rorke S, et al. Role of Cysteinyl Leukotrienes in Adenosine 5'-monophosphate Induced Bronchoconstriction in Asthma. Thorax. 2002;57(4):323-7. PubMed PMID: 11923550.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of cysteinyl leukotrienes in adenosine 5'-monophosphate induced bronchoconstriction in asthma. AU - Rorke,S, AU - Jennison,S, AU - Jeffs,J A, AU - Sampson,A P, AU - Arshad,H, AU - Holgate,S T, PY - 2002/3/30/pubmed PY - 2002/5/16/medline PY - 2002/3/30/entrez SP - 323 EP - 7 JF - Thorax JO - Thorax VL - 57 IS - 4 N2 - BACKGROUND: Adenosine induced bronchoconstriction in patients with asthma is thought to be mediated by the synthesis and release of autacoids from airway mast cells. In vitro, adenosine induced constriction of asthmatic bronchi is blocked by a combination of specific histamine and cysteinyl leukotriene receptor antagonists, but the relative contribution of these mediators in vivo is unclear. We hypothesised that adenosine induced bronchoconstriction in asthmatic patients may be blocked by pretreatment with the orally active selective cysteinyl leukotriene-1 (CysLT(1)) receptor antagonist, montelukast. METHODS: In a randomised, double blind, crossover study, oral montelukast (10 mg) or placebo was administered once daily on two consecutive days to 18 patients with mild to moderate persistent atopic asthma. Incremental doses of adenosine 5'-monophosphate (AMP) from 0.39 to 400 mg/ml were inhaled by dosimeter and the dose producing a 20% fall in FEV(1) (PC(20)AMP) after AMP inhalation was recorded. Leukotriene E(4) (LTE(4)) urinary concentrations were measured by enzyme immunoassay 4 hours after AMP challenge. RESULTS: Montelukast pretreatment provided highly significant protection against adenosine induced bronchoconstriction, with geometric mean PC(20)AMP values of 52.6 mg/ml (95% CI 35.2 to 78.7) after placebo and 123.9 mg/ml (95% CI 83.0 to 185.0) after montelukast (p=0.006). The geometric mean of the montelukast/placebo PC(20)AMP ratio was 2.4 (95% CI 1.3 to 4.2). Montelukast had no significant effect on 4 hour urinary excretion of LTE(4) compared with placebo. CONCLUSIONS: Selective CysLT(1) receptor antagonism with montelukast provides highly significant protection against AMP induced bronchoconstriction in patients with atopic asthma, implying that cysteinyl leukotrienes are generated from airway mast cells through preferential activation of their A(2B) receptors. SN - 0040-6376 UR - https://www.unboundmedicine.com/medline/citation/11923550/Role_of_cysteinyl_leukotrienes_in_adenosine_5'_monophosphate_induced_bronchoconstriction_in_asthma_ L2 - https://thorax.bmj.com/lookup/pmidlookup?view=long&pmid=11923550 DB - PRIME DP - Unbound Medicine ER -