The mechanism of action of leukotrienes A4, C4 and D4 on human lung parenchymain 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.