Evidence for opioid modulation and generation of prostaglandins in sulphur dioxide (SO)2-induced bronchoconstriction.
BACKGROUND
Inhalation of sulphur dioxide (SO2) provokes bronchoconstriction in asthmatic subjects. Cholinergic mechanisms contribute, but other mechanisms remain undefined. The effect of morphine, an opioid agonist, on the cholinergic component of SO2-induced bronchoconstriction was investigated, and the effect of indomethacin, a cyclooxygenase inhibitor, on SO2-induced bronchoconstriction and tachyphylaxis was studied.


METHODS
In the first study 16 asthmatic subjects inhaled either ipratropium bromide or placebo 60 minutes before an SO2 challenge on days 1 and 2. On day 3 an SO2 challenge was performed immediately after intravenous morphine. In the second study 15 asthmatic subjects took either placebo or indomethacin for three days before each study day when two SO2 challenges were performed 30 minutes apart. The response was measured as the cumulative dose causing a 35% fall in specific airways conductance (sGaw; PDsGaw35).


RESULTS
Ipratropium bromide significantly inhibited SO2 responsiveness, reducing PDsGaw35 by 0.89 (95% CI 0.46 to 1.31) doubling doses. This effect persisted after correction for bronchodilatation induced by ipratropium bromide. The effect of ipratropium bromide and morphine on SO2 responsiveness also correlated (r2 = 0.71). In the second study SO2 tachyphylaxis developed with PDsGaw35 on repeated testing, being reduced by 0.62 (95% CI 0.17 to 1.07) doubling doses. Indomethacin attenuated baseline SO2 responsiveness, increasing PDsGaw35 by 0.5 (95% CI 0.06 to 0.93) doubling doses.


CONCLUSIONS
These results suggest that opioids modulate the cholinergic component of SO2 responsiveness and that cyclooxygenase products contribute to the immediate response to SO2.
Field
P I
PI
Department of Thoracic Medicine, Royal North Shore Hospital, New South Wales, Australia.
Simmul
R
R
Bell
S C
SC
Allen
D H
DH
Berend
N
N
D000328:Adult; D001249:Asthma / Q000503:physiopathology*; D016084:Bronchoconstriction / Q000187:drug effects*; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D009241:Ipratropium / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000494:pharmacology; D011957:Receptors, Opioid / Q000819:agonists; D013458:Sulfur Dioxide / Q000494:pharmacology*
D016085:Bronchoconstrictor Agents; D016861:Cyclooxygenase Inhibitors; D011957:Receptors, Opioid; D013458:Sulfur Dioxide; D009020:Morphine; D009241:Ipratropium; D007213:Indomethacin