Role of substance P and neurokinin A in toluene diisocyanate-induced increased airway responsiveness in rabbits.
The aim of the present study was to examine the role of neuropeptides, especially substance P (SP) and neurokinin A (NKA), in toluene diisocyanate (TDI)-induced airway hyperresponsiveness (AHR) to acetylcholine aerosols. Thirty parts per billion of TDI in air administered over 4 hours caused a significant increase in the airway constrictive response to acetylcholine (ACH) aerosols in rabbits (DeltaRI: 245 +/- 30%, p < 0.005) without altering basic values of respiratory, cardiovascular or blood gas parameters. Inhalation of the aerosolized neuropeptides SP and NKA resulted in a similar increase in airway responsiveness (AR) to ACH as exposure to 30 ppb TDI. To determine whether neuropeptides contribute to TDI-induced AHR, we studied their effects after systemic treatment with capsaicin as well as after infusion of specific synthetic antagonists for SP and NK2 (NKA) receptors. CAPS treatment performed on 4 consecutive days as well as antagonists' infusion only moderately (p > 0.05) decreased airway responses to ACH. CAPS application prevented the TDI-induced increase in AR to ACH in all rabbits. The increase in airway resistance to ACH did not significantly change after TDI exposure (98 +/- 22% of the control response before TDI, p > 0.05). Simultaneous infusion of specific synthetic SP and NK2 receptor antagonists also abolished the TDI-induced increase in airway responses to ACH in all animals investigated (p > 0.05). The results of this study demonstrate that neuropeptides, especially the tachykinins SP and NKA, are important mediators in TDI-induced AHR in rabbits.
Marek
W
W
Professional Associations' Research Institute for Occupational Medicine, Ruhr University Bochum, Germany.
Potthast
J J
JJ
Marcynski
B
B
Baur
X
X
D000109:Acetylcholine / Q000494:pharmacology; D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D001980:Bronchi / Q000187:drug effects; D016084:Bronchoconstriction / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D004195:Disease Models, Animal; D008171:Lung Diseases / Q000139:chemically induced / Q000503:physiopathology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology*; D015288:Neurokinin A / Q000494:pharmacology / Q000502:physiology*; D064729:Neurokinin-1 Receptor Antagonists; D009784:Occupational Diseases / Q000139:chemically induced / Q000503:physiopathology*; D011817:Rabbits; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D013373:Substance P / Q000494:pharmacology / Q000502:physiology*; D014051:Toluene 2,4-Diisocyanate / Q000633:toxicity*; D014132:Trachea / Q000187:drug effects / Q000503:physiopathology
D064729:Neurokinin-1 Receptor Antagonists; D018041:Receptors, Neurokinin-2; D014051:Toluene 2,4-Diisocyanate; D013373:Substance P; D015288:Neurokinin A; D000109:Acetylcholine; D002211:Capsaicin