Release of epithelium-derived PGE2 from canine trachea after antigen inhalation.
To investigate the role of prostaglandin (PG) E2 in allergen-induced hyperresponsiveness, dogs inhaled either the allergen Ascaris suum or vehicle (Sham). Twenty-four hours after inhalation, some animals exposed to allergen demonstrated an increased responsiveness to acetylcholine challenge in vivo (Hyp-Resp), whereas others did not (Non-Resp). Strips of tracheal smooth muscle, either epithelium intact or epithelium denuded, were suspended on stimulating electrodes, and a concentration-response curve to carbachol (10(-9) to 10(-5) M) was generated. Tissues received electrical field stimulation, and organ bath fluid was collected to determine PGE2 content. With the epithelium present, all three groups contracted similarly to 10(-5) M carbachol, whereas epithelium-denuded tissues from animals that inhaled allergen contracted more than tissues from Sham dogs. In response to electrical field stimulation, Hyp-Resp tissues contracted less than Sham tissues in the presence of epithelium and more than Sham tissues in the absence of epithelium. PGE2 release in the muscle bath was greater in Non-Resp tissues than in Sham or Hyp-Resp tissues when the epithelium was present. Removal of the epithelium greatly inhibited PGE2 release. We conclude that tracheal smooth muscle is hyperresponsive in vitro after in vivo allergen exposure only when the modulatory effect of the epithelium, largely through PGE2 release, is removed.
McGrogan
I
I
Department of Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Janssen
L J
LJ
Wattie
J
J
O'Byrne
P M
PM
Daniel
E E
EE
D000280:Administration, Inhalation; D000485:Allergens / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D000947:Antigens, Helminth / Q000008:administration & dosage / Q000494:pharmacology; D017165:Ascaris suum; D001249:Asthma / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced*; D002217:Carbachol / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D004285:Dogs; D004558:Electric Stimulation; D004848:Epithelium / Q000276:immunology / Q000378:metabolism; D005260:Female; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010277:Parasympathomimetics / Q000494:pharmacology; D014132:Trachea / Q000276:immunology / Q000378:metabolism*
D000485:Allergens; D000947:Antigens, Helminth; D010277:Parasympathomimetics; D002217:Carbachol; D015232:Dinoprostone