Leukotriene transformation by guinea-pig lungs.

The metabolism of synthetic leukotrienes by guinea-pig lung homogenates was investigated. Leukotriene (LT) A4, B4, C4, D4 and E4 were incubated for various periods of time (0-180 min) at 37 degrees with guinea-pig lung homogenates (20,000 X g; 15 min) and the remaining biological activity was assayed either on guinea-pig ileum longitudinal smooth muscles (for LTA4, LTC4, LTD4 and LTE4) or on guinea-pig lung parenchymal strips (for LTB4 and on some occasions LTA4) in a cascade superfusion system. The half-life of LTD4 in our conditions was about 50 minutes but the inactivation plateaued after 120 minutes with approximately 25% of residual activity. When LTA4 and LTC4 were added to guinea-pig lung homogenates, increases of biological activity were measured during the first few min. (10 to 30 min) and were followed by decreases. The first activation period was probably due to rapid conversion to the more potent LTC4 and LTD4. LTB4 and LTE4 were not inactivated by guinea-pig lung homogenates (60-120 min). Inhibitors of lipoxygenases (eicosatetraynoic acid, ETYA; BW 755C; nordihydroguaiaretic acid, NDGA; phenidone) had no effect on LTD4 inactivation and on LTA4 transformation. gamma-glutamyl-O-carboxy-phenylhydrazide did not affect LTC4 activation. Our results confirmed the presence of the various enzymes responsible for both the formation and inactivation of leukotrienes in the guinea-pig lungs.