Do perfused small caliber airways of guinea-pig release an epithelium-dependent relaxing factor?
The influence of epithelium removal on the effects of contractile substances on airway responsiveness was investigated on the guinea-pig perfused bronchioles. A gentle rubbing of the luminal surface with a pipe cleaner significantly shifted to the left the concentration-response curves evoked by histamine (3 x 10(-12)-10(-4) M) and acetylcholine (10(-9)-10(-3) M) and decreased the relaxation response to fenoterol (10(-12)-2 x 10(-5) M). In contrast, removal of epithelium did not alter the responses to K+ (4.7 x 10(-3)-1.2 x 10(-1) M), theophylline (10(-8)-10(-2) M), sodium nitroprusside (4 x 10(-10)-4 x 10(-5) M) or papaverine (10(-4) M). In intact preparations treated with indomethacin (10(-5) M), histamine and acetylcholine induced contractions similar to that produced by rubbed tissues whereas relaxation induced by fenoterol was not modified. 10(-5) M tranylcypromine (inhibitor of prostacyclin synthesis) or 10(-6) M L-NAME (NG Nitro-L-Arginine Methyl Ester, a nitric oxide synthesis inhibitor) did not alter any concentration-response curves. Whereas prostaglandin E2 had no effect, prostaglandin E1 (10(-12)-10(-5) M) induced concentration-dependent relaxation, indicating that this prostanoid could be an epithelium-derived relaxing factor. These results suggest that epithelium of small caliber airways could release a cyclooxygenase product, namely a prostanoid, involved in the epithelium-dependent modulation in response to contractile drugs.
Burgaud
J L
JL
Laboratoire de Pharmacologie, UFR de Pharmacie, Limoges, France.
Javellaud
J
J
Oudart
N
N
D000818:Animals; D001685:Biological Factors / Q000378:metabolism*; D001980:Bronchi / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D005260:Female; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010477:Perfusion
D001685:Biological Factors; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; C056250:epithelium-derived relaxant factor; D007213:Indomethacin