Paf-induced release of spasmogens from guinea-pig lungs

1. The injection of platelet activating factor (Paf; 250 ng), leukotriene B4 (LTB4; 50 ng) and leukotriene D4 (LTD4; 10 ng) elicited contractions of strips of guinea-pig trachea, bronchus and lung parenchyma. 2. When the effluent of perfused guinea-pig lungs was superfused over strips of guinea-pig trachea, bronchus and parenchyma, the intra-arterial injection of Paf (250 ng) caused the release of spasmogen(s) which contracted all three tissues. 3. The infusion of indomethacin (10 micrograms ml-1) into the pulmonary artery and over the assay tissues inhibited the responses of the tissues to the effluent of the lungs stimulated by Paf (250 ng) and LTB4 (50 ng). However, treating only the assay tissues with indomethacin (10 micrograms ml-1) did not block the contractile responses to the effluent of the lungs stimulated with LTB4 or Paf. stimulated with Paf. 4. Pretreatment of the lungs with indomethacin (10 micrograms ml-1) or aspirin (30 micrograms ml-1) for 30 min, washing them out and suspending them over the assay tissues did not block the release of spasmogens elicited by Paf but appeared to inhibit the release of cyclo-oxygenase products. 5. The infusion of two lipoxygenase inhibitors, nordihydroguaiaretic acid (NDGA; 1 microgram ml-1) and L-655,240 (1 microgram ml-1), into the pulmonary artery completely blocked the release of spasmogen(s) from the perfused lungs. 6. The slow reacting substance of anaphylaxis (SRS-A) antagonist, FPL-55712 (10 ng ml-1), did not block the responses of the tissues to the spasmogen(s) release by Paf. 7. The infusion of the Paf antagonist BN-52021 (30 micrograms ml-1) into the pulmonary artery completely abolished the release of spasmogen(s) induced by Paf. 8. These data suggest that a lipoxygenase product, possibly LTB4, could be responsible for the spasmogenic activity released by the lungs following Paf stimulation. Cyclo-oxygenase products released following Paf stimulation appear to result from the initial LTB4 generation.