We examined an endogenous substance causing
cough in awake guinea pigs. An
intraperitoneal injection of
phosphoramidon, a selective inhibitor of
neutral endopeptidase (E.C. 3.4.24.11), caused
cough in a dose-dependent fashion for approximately 40 min. At a dose of 3 x 10(-3) mol/kg,
phosphoramidon caused a total of 11.6 +/- 1.4
coughs in 40 min.
Phosphoramidon (3 x 10(-3) mol/kg)-induced
cough was significantly inhibited by systemic pretreatment with
capsaicin (p < 0.01).
Aerosols of
FK 888 (1 min), a specific inhibitor of
substance P (NK1) receptor, inhibited
phosphoramidon (3 x 10(-3) mol/kg)-induced
cough in a dose-dependent fashion with complete inhibition at a dose of 10(-5) M. Likewise,
aerosols of
FK 224 (10(-5) M; 1 min), another inhibitor of NK1 and NK2 receptors, or
lidocaine (4%, 1 min) significantly inhibited
phosphoramidon (3 x 10(-3) mol/kg)-induced
cough (p < 0.01). Furthermore,
aerosols of
FK 888 (10(-5) M; 1 min) significantly inhibited
cough induced by cigarette
smoke in awake guinea pigs (p < 0.01). These results suggest that
substance P released from sensory nerves in the airway may be an endogenous substance causing
cough and the
substance P antagonist may be the
drug for treatment of
cough in respiratory disease.