Toluene diisocyanate contracts guinea pig bronchial smooth muscle by activating capsaicin-sensitive sensory nerves.
This study was designed to evaluate the mechanism of action of toluene diisocyanate (TDI) and the role of endogenous neutral endopeptidase in modulating in vitro contractile responses to TDI in guinea pigs. TDI (0.01-1 mM) produced a concentration-dependent contraction of the guinea pig main bronchi. Sensory nerve desensitization with capsaicin greatly reduced and in some cases almost abolished TDI-induced contractions. The neutral endopeptidase inhibitor phosphoramidon significantly increased the contractile response to TDI. Pretreatment with the substance P antagonist (D-Arg1,D-Pro2,D-Trp7,9,Leu11)-substance P greatly reduced TDI-induced contractions. These results suggest that TDI activates the "efferent" function of capsaicin-sensitive sensory nerves and that neutral endopeptidase may play a role in modulating the response in guinea pigs.
Mapp
C E
CE
Cardiovascular Research Institute, University of California, San Francisco.
Graf
P D
PD
Boniotti
A
A
Nadel
J A
JA
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology*; D006020:Glycopeptides / Q000494:pharmacology; D006168:Guinea Pigs; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009475:Neurons, Afferent / Q000187:drug effects*; D013373:Substance P / Q000494:pharmacology; D014051:Toluene 2,4-Diisocyanate / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D014051:Toluene 2,4-Diisocyanate; D013373:Substance P; D002211:Capsaicin; C008890:phosphoramidon