European journal of pharmacology
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Comparative Study
The role of substance P and bradykinin in the cough reflex and bronchoconstriction in guinea-pigs.
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. ⋯ 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.