Modulation of rabbit airway smooth muscle responsiveness by respiratory epithelium. Involvement of an inhibitory metabolite of arachidonic acid.
The integrity of the respiratory epithelium may be important in development of bronchial hyperreactivity; however, the mechanisms involved remain unknown. This study was undertaken to determine if epithelium of rabbit intrapulmonary bronchi is capable of modulating the responsiveness of airway smooth muscle to a pharmacologic stimulus, and whether epithelial-derived prostaglandins play a role in this modulatory function. Mechanical removal of the epithelium from bronchial segments, or incubation of intact bronchi with indomethacin (an inhibitor of prostaglandin synthesis) increased the sensitivity of bronchial smooth muscle to bethanechol. Cyclooxygenase was localized within mucosal epithelial cells of intact airways by avidin-biotin immunoperoxidase staining using a monoclonal antibody to the enzyme. Removal of the epithelium significantly reduced the levels of PGE2 and 6-keto-PGF1 alpha accumulated in the media surrounding bronchial explants. In epithelium-intact bronchi precontracted with bethanechol, arachidonic acid evoked an indomethacin-sensitive relaxation response comparable to relaxation induced by exogenous addition of PGE2. Although PGE2 evoked similar responses in epithelium-denuded bronchi, arachidonic acid-induced relaxation responses were negligible. The results suggest epithelial cells of rabbit bronchi modulate the responsiveness to pharmacologic stimuli by production and release of an inhibitory cyclooxygenase metabolite of arachidonic acid.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004848:Epithelium / Q000378:metabolism / Q000502:physiology; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000378:metabolism / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis; D011817:Rabbits
D001095:Arachidonic Acids; D001626:Bethanechol Compounds; D011453:Prostaglandins; D018723:Bethanechol; D016718:Arachidonic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin