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

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 PGF1α 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.