IngentaConnect Interactions of tachykinin receptor antagonists with lipopolysacc...

Authors: M Veron¹; I Guenon¹; S Nenan¹; X Emonds-Alt²; C Advenier³; V Lagente¹; E Boichot¹

Source: Clinical and Experimental Pharmacology and Physiology, Volume 31, Number 9, September 2004 , pp. 634-640(7)

Abstract:

Summary

1. Several observations suggest that tachykinins are involved in the pathogenesis of bronchopulmonary alterations. We have investigated the effect of antagonists for tachykinin NK₁ (SR 140333), NK₂ (SR 48968) or NK₃ (SR 142801) receptors on inflammatory cell recruitment, tumour necrosis factor (TNF)- agr

and interleukin (IL)-6 release and matrix metalloproteinase (MMP)-9 activity in the bronchoalveolar lavage fluid (BALF) of mice exposed to lipopolysaccharide (LPS; 100 µg/mL aerosol for 30 min).

2. Treatment of mice with a combination of SR 140333 and SR 48968 (10^-6 mol/L, aerosol) significantly reduced the increase in the number of total cells and neutrophils and MMP-9 activity in the BALF of mice 2.5 h after LPS exposure. Treatment with the NK₃ antagonist SR 142801 (10^-6 mol/L, aerosol) did not inhibit the influx of neutrophils, but markedly reduced the increase in TNF- agr

and IL-6 levels at 2.5 h and MMP-9 activity at 20 h.

3. These results show that the three tachykinin receptor antagonists may interfere with the development of airway inflammation, namely neutrophilia, TNF- agr

release or MMP-9 activity in the BALF of mice exposed to LPS and suggest that not only NK₁ and NK₂ receptors, but also NK₃ receptors are involved in the modulation of the inflammatory response and airway remodelling.

Keywords: airway inflammation; lipopolysaccharide; metalloproteinase; mice; SR 142801; tachykinin

Document Type: Research article

DOI: 10.1111/j.1440-1681.2004.04061.x

Affiliations: 1: Faculté de Pharmacie, Université de Rennes 1, Rennes, 2: Sanofi-Synthélabo recherche Montpellier and 3: UPRES-EA220-Pharmacologie, UFR Biomédicale des Saints-Pères, Université Paris V, Paris, France

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Interactions of tachykinin receptor antagonists with lipopolysaccharide-induced airway inflammation in mice