ROLE OF SUBSTANCE-P IN COUGH DURING BRONCHOCONSTRICTION IN AWAKE GUINEA-PIGS

To examine the role of substance P (SP) in cough during bronchoconstri ction, we studied the effects of an aerosolized beta-adrenoceptor agon ist, procaterol, and a specific inhibitor of SP (NK1) receptor, FK 888 , on bronchoconstriction and cough induced by aerosols of histamine an d acetylcholine (ACh) in unsensitized guinea pigs and by those of oval bumin (OA) antigen in guinea pigs sensitized to OA. Intensity of bronc hoconstriction was evaluated by the time to onset of bronchoconstricti on 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 depe ndently decreased the number of coughs and increased the time to onset of bronchoconstriction induced by histamine (10(-2) M, 15 s). Procate rol attenuated histamine-induced cough only at the concentrations effe ctive to inhibit bronchoconstriction. However, FK 888 at concentration s of 10(-7) and 10(-6) M decreased the number of coughs without effect on bronchoconstriction. Likewise, the inhibitory effects of procatero l (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 nu mber of coughs without effect on bronchoconstriction induced by them. The number of coughs induced by histamine (10(-2) M, 15 s) was inhibit ed by systemic capsaicin treatment and enhanced by phosphoramidon (10( -5) M, 5 min) without effect on bronchoconstriction. These results sug gest that a beta-adrenoceptor agonist inhibits cough predominantly via a bronchodilating action, and SP released from sensory nerves may med iate cough during bronchoconstriction.