The mechanism of action of leukotrienes A4, C4 and D4 on human lung parenchyma in vitro

Indomethacin (20µg.ml−1), a cyclooxygenase inhibitor, and OKY-1581 (50 ug.ml−1), a thromboxane synthetase inhibitor, did not affect contractions of the superfused human lung parenchymal strips induced by histamine, leukotriene C4 (LTC4) and leukotriene D4 (LTD4). Indomethacin but not OKY-1581 reduced by 50% the myotropic activity of leukotriene A4 (LTA4) on the human lung strips. Injections of LTD4 (100 ng; 0.2 n mole) in the circulation of perfused specimens of human lung did not stimulate the release of prostaglandins (PGs) and thromboxanes (TXs) whereas they produced a large release of these icosanoids from perfused guinea-pig lungs. Perfused human lung specimens almost completely inactivated intraarterial injections of PGE2 (50 ng) and released PGs and TXs upon mechanical stimulation. It is concluded that the actions of leukotrienes C4 and D4 in human lung (parenchymal strips and perfused specimens) are not mediated by the release of PGs and TXs.