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

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.

• Authors: S Tomari, T Shimoda, T Kawano, K Mitsuta, Y Obase, H Matsuse, C Fukushima, S Kohno
• Journal: International archives of allergy and immunology (Int Arch Allergy Immunol) Vol. 123 Issue 2 Pg. 155-61 (Oct 2000) ISSN: 1018-2438 [Print] Switzerland
• PMID: 11060488 (Publication Type: Journal Article)

Chemical References

• Air Pollutants
• Cyanates
• Isocyanates
• Muscarinic Antagonists
• Receptors, Muscarinic
• 1,6-hexamethylene diisocyanate
• Atropine
• Acetylcholine

Topics

• Acetylcholine (analysis)
• Air Pollutants (pharmacology)
• Animals
• Asthma (chemically induced)
• Atropine (pharmacology)
• Cyanates (adverse effects, antagonists & inhibitors, pharmacology)
• Dogs
• Dose-Response Relationship, Drug
• Isocyanates
• Muscarinic Antagonists (pharmacology)
• Muscle Contraction (drug effects)
• Muscle, Smooth (drug effects, metabolism)
• Occupational Diseases (chemically induced)
• Receptors, Muscarinic (drug effects)
• Trachea (drug effects)