Leukotriene F4 and the release of arachidonic acid metabolites from perfused guinea pig lungs in vitro

Radioimmunoassay and bioassay techniques have been used to investigate the ability of leukortriene (LT)F₄ to release products of arachidonic acid metabolism from guinea pig isolated lungs perfused via the pulmonary artery. Also, the abilities of LTC₄, LTD₄ LTE₄ and LTE₄ to contract guinea pig ileal smooth muscle (GPISM) was studied. Each of the LT's contracted GPISM. The rank order of potency was LTD₄ > LTC₄ > LTE₄ > > LTF₄ in a ratio 1:7:170:280 respectively. Bioassay of pulmonary effluents indicated the passage of LTF₄ through the lungs caused a contraction of rabbit aorta as well as an FPL-55712 sensitive contraction of GPISM. The contractions of rabbit aorta were inhibited by pretreatment of the lungs with Indomethacin but not with the thromboxane synthetase inhibitor Dazoxiben. Radioimmunoassay of the lung effluents indicated LTF₄ to cause a 70-fold increase in thromboxane B₂ (TXB₂), 4-fold increase in prostaglandin (PG)E₂ and a 16-fold increase in 6-keto PGF_1α levels. The LTF₄-induced increments of these immunoreactive metabolites was inhibited by pretreatment of the lungs with Indomethacin. Pretreatment of lungs with Dazoxiben inhibited the LTF₄-induced increment in TXB₂ and enhanced the effluet levels of PGE₂ 24-fold (compared with untreated lungs). There were no detectable differences in either immunoreactive LTC₄ or immunoreactive LTB₄ levels. It is concluded LTF₄ is a relatively weak agonist on GPISM and can induce the release of cyclooxygenase products of arachidonic acid metabolism from guinea pig perfused lung.