In this study we investigated the ability of aerosolized
substance P to induce either
cough or bronchoconstriction in guinea-pigs. We have also examined whether pre-treatment, by the inhaled route, of animals with a combination of the
neutral endopeptidase inhibitor,
phosphoramidon (10(-3) M), and the diaminopeptidase IV inhibitor,
diprotin A (10(-3) M), enhances the airway response to
substance P. Moreover, we also assessed whether
aerosol pre-treatment of guinea-pigs with either
substance P or
bradykinin,
at 10(-4) M, affects the
citric acid-induced
cough and/or bronchoconstriction. Challenge of guinea-pigs with
substance P only
at 10(-3) M resulted in significant bronchconstriction but only a weak and variable
cough response (1.1+/-0.6; P>0.05). Pre-treatment of guinea-pigs with both
phosphoramidon and
diprotin A resulted in a small non-significant increase in the
cough response (2.8+/-0.9 vs. 1.1+/-0.6; P>0.05) but significantly enhanced
substance P-induced bronchoconstriction (P<0.05). Moreover, exposure of guinea-pigs to
substance P (10(-4) M) prior to
citric acid challenge (0.6 M) resulted in a significant (P<0.05) enhancement of the
citric acid-induced bronchoconstriction but not the
citric acid-induced
cough (11.7+/-1.8 vs. 12.8+/-1.5; P>0.05). In contrast, exposure of guinea-pigs to
bradykinin (10(-4) M) prior to the
citric acid challenge resulted in a significant enhancement of the
cough response (9.2+/-1.9 vs. 25.8+/-2.5; P<0.05) but not the bronchoconstriction (P>0.05). These data do not support a major peripheral role for
substance P in the
cough reflex, although
bradykinin is able to sensitize the
cough reflex. Furthermore, these data suggest that bronchoconstriction, induced by
citric acid, is not responsible for the
cough associated with this
irritant.