Am. J. Respir. Crit. Care Med., Vol 151, No. 3, Mar 1995, 815-821.
Role of substance P in cough during bronchoconstriction in awake guinea pigs
K Sekizawa, T Ebihara and H Sasaki
Department of Geriatric Medicine, Tohoku University School of Medicine, Sendai, Japan.
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)
