neurokinin-a and Lung-Diseases

Topics: Animals; Central Nervous System Diseases; Drug Combinations; Gastrointestinal Diseases; Humans; Lung Diseases; Neurokinin A; Neurokinin B; Pain; Receptors, Tachykinin; Substance P; Urologic Diseases; Vomiting

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.

Topics: Acetylcholine; Administration, Inhalation; Airway Resistance; Animals; Bronchi; Bronchoconstriction; Capsaicin; Disease Models, Animal; Lung Diseases; Muscle, Smooth; Neurokinin A; Neurokinin-1 Receptor Antagonists; Occupational Diseases; Rabbits; Receptors, Neurokinin-2; Substance P; Toluene 2,4-Diisocyanate; Trachea