To examine the role of
substance P (SP) in
cough during bronchoconstriction, we studied the effects of an aerosolized beta-
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. (ABSTRACT TRUNCATED AT 250 WORDS)