Evidence for a mediator role of thromboxane A2 in the myotropic action of leukotriene B4 (LTB4) on the guinea-pig lung.

The mechanism of action of LTB4 has been investigated on the guinea-pig lung parenchymal strip. Mepacrine (20 microgram/ml), an inhibitor of phospholipase A2, abolished the action of LTB4 on parenchymal strips. Eicosatetraynoic acid (10 microgram/ml) and BW755C (40 microgram/ml) which are inhibitors of cyclooxygenase and lipoxygenase pathways, produced a marked inhibition of the lung strip contraction to LTB4. Similarly, aspirin (30 micrograms/ml) and flufenamate (1 microgram/ml) showed a strong inhibition of the contraction of parenchymal strips to LTB4; these results suggested that cyclooxygenase products mediate the action of LTB4. The response to LTB4 was unaffected by 15-hydroperoxyeicosatatraenoic acid (15-HPETE; 1 microgram/ml) while L8027 (25 ng/ml) reduced the contraction by 50%, suggesting that thromboxane A2 rather than prostacyclin was involved. Since parenchymal strips do not appear to be very sensitive to PGF2 alpha, PGE2 and the endoperoxides, and since effluents from LTB4-treated lungs produced contractions of lung strip and rabbit aorta which were reduced after 5 min. at 25 degrees, thromboxane A2 was postulated to mediate the lung effect of LTB4. The release of thromboxane B2 (TxB2) from lungs stimulated with LTB4 was confirmed by gas-chromatography-mass spectrometric (GC-MS) analyses.