Indian J Pharmacol. 2011 Jul;43(4):445-9. doi: 10.4103/0253-7613.83119.

Effect of Montelukast on bradykinin-induced contraction of isolated tracheal smooth muscle of guinea pig.

Indian journal of pharmacology

A Noor, M H Najmi, S Bukhtiar

PMID: 21845003 PMCID: PMC3153711 DOI: 10.4103/0253-7613.83119

Abstract

AIM: To explore the effect of montelukast on bradykinin-induced tracheal smooth muscle contraction of isolated guinea pig trachea.

STUDY DESIGN: To study the effect of bradykinin in the absence and in the presence of montelukast on the isolated tracheal smooth muscle of a guinea pig pretreated with indomethacin (10(-6)M), phentolamine (10(-5)M), and propranalol (10(-6)M), to eliminate the effect of endogenous prostaglandins and catecholamines. The trachealis smooth muscle activity was recorded through the Isometric Force Displacement Transducer on a Four Channel Oscillograph. A cumulative dose-response relationship was demonstrated by adding successive doses of bradykinin on the tracheal strips, starting with 11 μg to 77 μg of 10(-4) concentration. A similar procedure was repeated in the presence of montelukast 0.5 μg/ml, which, was equal to approximate C(max) achieved in vivo with a 10 mg oral dose of montelukast, and in the presence of 1 μg/ml of montelukast.

STATISTICAL ANALYSIS: Data was expressed as mean ± standard error (SEM), and was analyzed using the SPSS version 15. A P value of less than 0.05 was considered significant.

RESULTS: Bradykinin produced a dose-dependent, reversible contraction of isolated tracheal smooth muscle. Montelukast significantly reduced the bradykinin-induced tracheal smooth muscle reactivity and shifted the bradykinin curve to the right and downwards, in the presence of both concentrations of montelukast. The mean magnitude of response achieved with 77 μg of bradykinin in the absence of montelukast was 39 mm ± 6.26, in the presence of 0.5 μg/ml of montelukast it was 24.17 mm ± 4.11, and in the presence of 1 μg/ml of montelukast it was 13 mm ± 2.6.

CONCLUSION: It is concluded that montelukast significantly inhibits, in a dose-dependent manner, the bradykinin-induced contraction of the guinea pig tracheal smooth muscle, and alludes to an interaction between the bradykinin and leukotriene mediators.

Keywords: ACE inhibitors; bradykinin; cough; guinea pig trachea; montelukast

References

1. Jpn J Pharmacol. 1999 Apr;79(4):403-26 - PubMed
2. Eur Respir J. 1993 Apr;6(4):576-87 - PubMed
3. Biochem Biophys Res Commun. 2004 Nov 12;324(2):815-21 - PubMed
4. Eur J Pharmacol. 2003 Jan 1;458(1-2):175-81 - PubMed
5. Pulm Pharmacol. 1996 Oct-Dec;9(5-6):323-8 - PubMed
6. J Asthma. 2002 Jun;39(4):291-7 - PubMed
7. Br J Clin Pharmacol. 1995 Mar;39(3):265-70 - PubMed
8. Agents Actions. 1990 Nov;31(3-4):204-9 - PubMed
9. J Allergy Clin Immunol. 2002 Feb;109(2):195-209 - PubMed
10. Br J Pharmacol. 1997 Oct;122(3):417-22 - PubMed
11. Allergol Int. 2008 Dec;57(4):441-3 - PubMed
12. Pulm Pharmacol Ther. 2000;13(4):181-8 - PubMed
13. Am J Respir Crit Care Med. 2003 Feb 1;167(3):379-83 - PubMed
14. J Pharmacol Exp Ther. 1999 May;289(2):682-7 - PubMed
15. J Appl Physiol Respir Environ Exerc Physiol. 1984 Aug;57(2):457-66 - PubMed
16. J Pharmacol Exp Ther. 1988 Feb;244(2):531-6 - PubMed
17. Biopharm Drug Dispos. 1997 Dec;18(9):769-77 - PubMed
18. Am J Respir Cell Mol Biol. 2000 Jan;22(1):75-84 - PubMed
19. J Allergy Clin Immunol. 2005 Apr;115(4):870-2 - PubMed
20. Am J Respir Crit Care Med. 1996 Mar;153(3):918-23 - PubMed

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