Myogenic and neurogenic mechanisms and arachidonate metabolites in bronchial muscle response to allergen.
We investigated allergen-induced airway hyperresponsiveness (AH) in bronchial tissues obtained from dogs that inhaled Ascaris suum leading to AH (RESP) in vivo or that exhibited no change (NON-RESP) as well as from dogs that inhaled saline (SHAM). RESP tissues were not hyperresponsive to KCl or to carbachol, whereas contractions to electrical field stimulation (EFS) were reduced. This reduction was reversed partially by indomethacin and completely by replacement of the bathing fluid. Radioimmunoassay revealed marked elevation of prostaglandin (PG) E2 generation in RESP tissues compared with SHAM and NON-RESP tissues. EFS-evoked contractions were often followed by a slowly developing secondary contraction in RESP tissues but not in SHAM or NON-RESP tissues. However, indomethacin unmasked such secondary contractions in many SHAM and NON-RESP tissues and markedly enhanced those in RESP tissues, whereas L-655,240 (thromboxane A2/PGD2 receptor antagonist) abolished such contractions in all groups. We were unable to detect thromboxane using radioimmunoassay. We conclude that allergen-induced AH involves altered generation of cyclooxygenase metabolites of arachidonic acid (particularly PGE2) as well as of a nonprostanoid inhibitory factor; as such, the responsiveness of the tissue in vitro is dependent on the relative levels of inhibitory and excitatory metabolites.
Janssen
L J
LJ
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
McGrogan
I
I
Wattie
J
J
O'Byrne
P M
PM
Daniel
E E
EE
D000485:Allergens; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D017165:Ascaris suum; D001980:Bronchi / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D002217:Carbachol / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology
D000485:Allergens; D001095:Arachidonic Acids; D011189:Potassium Chloride; D002217:Carbachol; D009543:Nifedipine; D015232:Dinoprostone; D007213:Indomethacin