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  • Title: Hexamethylene diisocyanate causes contraction of canine tracheal smooth muscles through activation of muscarinic receptors.
    Author: Tomari S, Shimoda T, Kawano T, Mitsuta K, Obase Y, Matsuse H, Fukushima C, Kohno S.
    Journal: Int Arch Allergy Immunol; 2000 Oct; 123(2):155-61. PubMed ID: 11060488.
    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 EC(50) (HDI concentration that produced 50% of the maximal response) was 6.2+/-0.7 x10(-7) M and the maximal contractile response (174+/-55 g/g of tissue) occurred at a concentration of 5.0+/-0.8 x 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 pA(2) 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.
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