Source: Annual Congress 2002 - Bronchial responsiveness in asthma and COPD
Disease area: Airway diseases

Abstract

Activation of sensory nerves, via VRs, results in a variety of inflammatory responses in the airways, such as bronchoconstriction, plasma extravasation and cough. Protons are known to activate these neurones, via activation of the VR1 and these actions can be mimicked with the use of inhaled citric acid. In this study, we have investigated the effect of a new and ultra-potent VR1 antagonist, Iodo-Resiniferatoxin (I-RTX), on a guinea pig model of cough. Pre-treatment with I-RTX (30 and 100 nmol/kg-1, i.p. 10 min prior) inhibited the cough response (coughs/10 min) in conscious guinea pigs to citric acid (0.25 M, 10 min) from 11.8 ±] 1.2 in control animals to 6 ±] 0.4 and 4 ±] 1.1 (P < 0.05, n > 6), respectively. The threshold dose of I-RTX (i.p.) against citric acid induced cough was 30 nmol/kg-1.When compared to capsazepine (CPZ, i.p.), I-RTX was at least 100 times more potent at inhibiting cough (Fig. 1).Furthermore, nebulized I-RTX significantly attenuated both citric acid and capsaicin induced cough (Fig. 2), showing a similar degree of efficacy to I-RTX administered i.p.This studies provide compelling evidence of the antitussive qualities of VR1 antagonists. Furthermore, this new antagonist has been demonstrated in vivo to be 100 fold more potent than CPZ, thus posing the possibility of investigating VR1 receptors more thoroughly in in vivo settings.

Supported: ARCA & MURST

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Citations should be made in the following way:
M. Trevisani, A. Milan, A. Zanasi, P. Geppetti, S. Harrison (Ferrara, Bologna, Italy). A new ultra-potent vanilloid receptor 1 (VR1) antagonist abates capsaicin and citric acid induced cough. Eur Respir J 2002; 20: Suppl. 38, 1206

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