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Role of substance P and neurokinin A in toluene diisocyanate-induced increased airway responsiveness in rabbits

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Abstract

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 (ΔRI: 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.

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Authors and Affiliations

  1. Professional Associations' Research Institute for Occupational Medicine (BGFA), Department of Pathophysiology and Toxicology, Institute at the Ruhr University Bochum, Bürkle-de-la-Camp-Platz 1, D-44789, Bochum, Germany

    W. Marek, J. J. W. Potthast, B. Marczynski & X. Baur

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  1. W. Marek
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  2. J. J. W. Potthast
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  3. B. Marczynski
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  4. X. Baur
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Offprint requests to: Dr. rer. nat. Wolfgang Marek

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Marek, W., Potthast, J.J.W., Marczynski, B. et al. Role of substance P and neurokinin A in toluene diisocyanate-induced increased airway responsiveness in rabbits. Lung 174, 83–97 (1996). https://doi.org/10.1007/BF00177703

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