A comparative study of the effects of citric acid, capsaicin and resiniferatoxin on the cough challenge in guinea-pig and man.
The cough response following inhalation challenge with the sensory nerve irritant resiniferatoxin was compared with that of capsaicin and citric acid in guinea-pig and man. Capsaicin and citric acid gave comparable dose-response curves in the two species. The mean (+/- SEM) concentration producing five coughs in man was 141.3 (1.3) mM (n = 10) for citric acid and 2.8 (1.3) microM (n = 10) for capsaicin. Those for the guinea-pig were 74.1 (1.2) mM (n = 10) for citric acid and 6.0 (2.4) microM (n = 10) for capsaicin. Resiniferatoxin was active at a lower concentration than either citric acid or capsaicin and maximal tolerable cough response was achieved at concentrations of 3 microM (n = 5) in guinea-pig and 300 nM (n = 1) in man. The cough response to resiniferatoxin was greatly prolonged in both guinea-pig and man. Resiniferatoxin, like capsaicin, caused respiratory distress in the guinea-pig which is linked to bronchoconstriction. Resiniferatoxin probably causes cough by stimulation of capsaicin sensitive neurones.
Laude
E A
EA
University Department of Medicine, Royal Hallamshire Hospital, Sheffield, UK.
Higgins
K S
KS
Morice
A H
AH
D000280:Administration, Inhalation; D000328:Adult; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology*; D002951:Citrates / Q000494:pharmacology*; D019343:Citric Acid; D003371:Cough / Q000139:chemically induced* / Q000503:physiopathology; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004417:Dyspnea / Q000139:chemically induced / Q000503:physiopathology; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D008875:Middle Aged; D012018:Reflex / Q000187:drug effects; D012119:Respiration / Q000187:drug effects; D012129:Respiratory Function Tests
D002951:Citrates; D004224:Diterpenes; D019343:Citric Acid; C024353:resiniferatoxin; D002211:Capsaicin