Role of Substance P in Cough during Bronchoconstriction in Awake Guinea Pigs

Abstract To examine the role of substance P (SP) in cough during bronchoconstriction, we studied the effects of an aerosolized χ-adrenoceptor agonist, procaterol, and a specific inhibitor of SP (NK1) receptor, FK 888, on bronchoconstriction and cough induced by aerosols of histamine and acetylcholine (ACh) in unsensitized guinea pigs and by those of ovalbumin (OA) antigen in guinea pigs sensitized to OA. Intensity of bronchoconstriction was evaluated by the time to onset of bronchoconstriction after the inhalation of bronchoconstrictors. Both procaterol (10−6 to 10−4 M, 2 min) and FK 888 (10−7 to 10−5 M, 2 min) dose dependently decreased the number of coughs and increased the time to onset of bronchoconstriction induced by histamine (10−2 M, 15 s). Procaterol attenuated histamine-induced cough only at the concentrations effective to inhibit bronchoconstriction. However, FK 888 at concentrations of 10−7 and 10−6 M decreased the number of coughs without effect on bronchoconstriction. Likewise, the inhibitory effects of procaterol (10−5 M, 2 min) on the number of coughs were parallel to those on bronchoconstriction induced by ACh (10−1 M, 15 s) and OA antigen (0.1% concentration, 30 s), but FK 888 (10−6 M, 2 min) decreased the number of coughs without effect on bronchoconstriction induced by them. The number of coughs induced by histamine (10−2 M, 15 s) was inhibited by systemic capsaicin treatment and enhanced by phosphoramidon (10−5 M, 5 min) without effect on bronchoconstriction. These results suggest that a β-adrenoceptor agonist inhibits cough predominantly via a bronchodilating action, and SP released from sensory nerves may mediate cough during bronchoconstriction.