Hexamethylene diisocyanate causes contraction of canine tracheal smooth muscles through activation of muscarinic receptors.
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.
Tomari
S
S
The Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
Shimoda
T
T
Kawano
T
T
Mitsuta
K
K
Obase
Y
Y
Matsuse
H
H
Fukushima
C
C
Kohno
S
S
D000109:Acetylcholine / Q000032:analysis; D000393:Air Pollutants / Q000494:pharmacology*; D000818:Animals; D001249:Asthma / Q000139:chemically induced; D001285:Atropine / Q000494:pharmacology; D003485:Cyanates / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D017953:Isocyanates; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D009784:Occupational Diseases / Q000139:chemically induced; D011976:Receptors, Muscarinic / Q000187:drug effects*; D014132:Trachea / Q000187:drug effects
D000393:Air Pollutants; D003485:Cyanates; D017953:Isocyanates; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; C015262:1,6-hexamethylene diisocyanate; D001285:Atropine; D000109:Acetylcholine