Inhibition by capsazepine of cough induced by capsaicin and citric
acid, but not by hypertonic saline in awake guinea pigs.
Lalloo, Umesh G., Alyson J. Fox, Maria G. Belvisi, K. Fan Chung, and
Peter J. Barnes.
Department of Thoracic Medicine, National Heart and Lung Institute,
Dovehouse Street, London SW3 6LY, United Kingdom
APStracts 2:0243A, 1995.
Acidic solutions mimick many of the effects of capsaicin, including
pain, bronchoconstriction, cough and sensory neuropeptide release.
Evidence from the use of the capsaicin antagonist capsazepine suggest
that in some cases protons act at the capsaicin receptor. In the
present study we have investigated whether cough evoked by capsaicin
and citric acid is mediated specifically via the capsaicin receptor
on airway sensory nerves. We have examined the effects of capsazepine
on capsaicin-, citric acid- and hypertonic saline-induced cough, and
also citric acid-induced nasal irritation, in awake guinea pigs.
Capsazepine was nebulized for 5 min prior to cough challenges with
capsaicin for 5 min and citric acid for 10 min. Control animals were
pre-treated with vehicle alone. Capsazepine (100[mu]M) inhibited the
cough response to 30[mu]M capsaicin from 0.77+/-0.14 coughs/min in
control animals to 0.23+/-0.08 coughs/min (P<0.05), and to
80[mu]M capsaicin from 1.4+/-0.23 coughs/min to 0.3+/-0.11 coughs/min
(P<0.01). There was no effect however of lower concentrations of
capszepine (5[mu]M and 10[mu]M) against capsaicin-evoked cough. At a
concentration of 100[mu]M capsazepine also inhibited the coughing
induced by 0.25M citric acid from 1.8+/-0.26 coughs/min to 0.93+/
-0.31 coughs/min (P<0.05), but not that induced by 0.5M citric
acid. Nasal irritation induced by 0.25M citric acid, but not by 0.5M
citric acid, was also inhibited by capsazepine from 2.47+/-0.37 nose
wipes/min to 0.75+/-0.31 nose wipes/min (P<0.05). This
inhibitory effect of capsazepine did not appear to reflect a non
-specific suppression of the cough reflex, since cough evoked by
exposure to hypertonic (7%) saline for 10 min was unaffected by pre
-treatment with capsazepine (100[mu]M). These data show that
capsazepine is a specific inhibitor of capsaicin- and citric acid
-induced cough in guinea pigs. Moreover they suggest that low pH
stimuli evoke cough and nasal irritation by an action at the
capsaicin receptor, either directly or through the release of an
intermediate agent.
Received 7 February 1995; accepted in final form 23 May 1995.
APS Manuscript Number A143-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 July 1995.