RELEASE AND ACTIONS OF INHIBITORY PROSTAGLANDINS FROM CANINE TRACHEALEPITHELIUM

This study evaluated the sources and actions of inhibitory prostanoids on canine tracheal smooth muscle to determine if these accounted for epithelium derived relaxing factor activity. Concentration-response cu rves of canine tracheal smooth muscle were generated to carbachol in t he presence and absence of the epithelium and (or) indomethacin, a cyc looxygenase inhibitor. Removal of the epithelium or addition of indome thacin (10(-5) M) in the presence of the epithelium shifted the curve significantly leftward compared with epithelial-intact tissue. Further more, addition of indomethacin to epithelial-denuded tissue produced t he greatest shift in the curve. Removal of the epithelium increased co ntractility in response to electrical-field stimulation at intermediat e frequencies compared with epithelium-intact tissues. The addition of indomethacin to epithelium-intact tissue also increased the contracti le responses. Removal of the epithelium in the presence of indomethaci n further increased responses. Radioimmunoassay of muscle bath fluid i ndicated that the inhibitory prostanoids prostaglandin I-2 (PGI(2)) an d prostaglandin E(2) (PGE(2)) were released. PGI(2) was released from the epithelium as well as from a nonepithelial source. PGE(2) was rele ased from the epithelium in response to electrical-field stimulation. The release of PGE(2) was greatly reduced by the addition of indometha cin (10(-5) M), but not by the addition of omega-conotoxin (GVIA), an N-type Ca2+ channel antagonist, nor by the addition of tetrodotoxin, a Na+ channel blocker. Both toxins abolished contractions to electrical -field stimulation. We conclude that the inhibitory prostanoids PGI(2) and PGE(2) are released, along with a nonprostanoid factor from epith elium, and modulate airway smooth muscle contractility to stimulation of cholinergic nerves and muscarinic agonists. PGE(2) is released from epithelium by electrical-field stimulation independent of nerve funct ion.