Prostacyclin modulates the responses to leukotrienes C4 and D4 of guinea-pig airway smooth muscle

Superfusion of lung parenchymal strips or tracheal strips from the guinea-pig with effluent from perfused isolated lungs reduced the contractions elicited by leukotriene C4 (LTC4) and leukotriene D4 (LTD4) but not those elicited by acetylcholine (ACh). Incubation of the lung perfusate for 15 min at 37 degrees C removed the inhibitory effect, as did treatment of the lungs with indomethacin (0.5 microgram ml-1) suggesting that a labile cyclo-oxygenase product was causing the inhibition. Addition of prostacyclin (0.8-5.0 ng ml-1) to the fluid superfusing tracheal and parenchymal strips produced a dose-related decrease in leukotriene-induced contractions, whereas 6-oxo-PGF1 alpha and PGE2 were inactive. Contractions of tracheal strips induced by LTC4 were significantly enhanced by infusion of PGF2 alpha. Parenchymal strips usually developed tachyphylaxis to repeated doses of LTC4. This tachyphylaxis has less evident in the presence of indomethacin (2 micrograms ml-1). Contractions of parenchymal and tracheal strips to histamine, acetylcholine and the stable thromboxane mimetic U-46619 were unaffected by infusion of prostacyclin (5 ng ml-1). These results indicate that prostacyclin selectively antagonises airway smooth muscle reactivity to LTC4 and LTD4 by a mechanism which remains to be elucidated.