Hexamethylene diisocyanate causes contraction of canine tracheal smooth muscles through activation of muscarinic receptors.

Publisher Website
Google Scholar
Abstract
Background: Asthma caused by occupational exposure to hexamethylene diisocyanate (HDI) is well known; however, the exact pathogenic mechanisms remain unclear. Methods: Experiments were performed using a standard canine tracheal smooth muscle (CTSM) strip preparation in an isolated bath to determine the effect of HDI on tracheal smooth muscle contraction. HDI concentration-response curves were constructed and the effects of different receptor antagonists on HDI-induced smooth muscle contraction were determined. To determine whether HDI and acetylcholine (ACh) bind to a common muscarinic receptor, ACh concentration-response curves in the absence or presence of HDI and concentration-response curves for HDI and ACh in the presence or absence of atropine were plotted. Results: HDI caused contraction of CTSM, with a threshold concentration of 10–7 M. The EC50 (HDI concentration that produced 50% of the maximal response) was 6.2 ± 0.7 × 10–7 M and the maximal contractile response (174 ± 55 g/g of tissue) occurred at a concentration of 5.0 ± 0.8 × 10–6 M. Atropine, a muscarinic blocker, significantly inhibited HDI-induced contractile responses. HDI shifted the ACh concentration-response curve to the right. The mean pA2 for atropine against ACh (8.93 ± 0.27) was not significantly different from that against HDI (8.03 ± 0.12). Conclusions: Our results indicated that HDI causes contraction of CTSM through the activation of muscarinic receptors. Direct stimulation of muscarinic receptors by HDI may play an important role in HDI-induced asthma.

This publication has 0 references indexed in Scilit: