Evidence for substance P as an endogenous substance causing cough in guinea pigs.
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.
Ujiie
Y
Y
Department of Geriatric Medicine, Tohoku University School of Medicine, Sendai, Japan.
Sekizawa
K
K
Aikawa
T
T
Sasaki
H
H
D000336:Aerosols; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D003371:Cough / Q000139:chemically induced / Q000503:physiopathology*; D004151:Dipeptides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006020:Glycopeptides / Q000008:administration & dosage; D006168:Guinea Pigs; D007211:Indoles / Q000494:pharmacology; D008297:Male; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000502:physiology; D012907:Smoking / Q000009:adverse effects; D013373:Substance P / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D015320:Tachykinins / Q000037:antagonists & inhibitors
D000336:Aerosols; D004151:Dipeptides; D006020:Glycopeptides; D007211:Indoles; D015320:Tachykinins; C078949:FK 888; D013373:Substance P; D015260:Neprilysin; D002211:Capsaicin; C008890:phosphoramidon