Inhibition of inflammatory cell recruitment by the tachykinin NK3-receptorantagonist, SR 142801, in a murine model of asthma

Several observations suggest that tachykinins (substance P, neurokinin A an d neurokinin B) are involved in the pathogenesis of pulmonary diseases and elicit several airway responses such as bronchoconstriction and neurogenic inflammation via interactions with specific receptors denoted NK,, NK, and NK,. We have investigated the effect of a selective antagonist for tachykin in NK, receptor. SR 142801 ((R)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl) piperidin-3-yl)propyl)-4-phenylpiperidin-4-yl-N-methylacetamide)), on the i nflammatory cell recruitment in ovalbumin-sensitized acid -challenged mice used as a model of allergic asthma. Twenty hours after the two-ovalbumin ch allenges, differential cell counts were calculated and indicated that SR 14 2801 caused a significant decrease in the number of neutrophils and eosinop hils. Forty hours after the last ovalbumin exposure, SR 142801 induced a si gnificant decrease in the recruitment of eosinophils. These results suggest that tachykinins and tachykinin NK, receptors can interfere with cell recr uitment in inflammatory response. (C) 2001 Elsevier Science B.V. All rights reserved.