Differential release of eicosanoids by bradykinin, arachidonic acid and calcium ionophore A23187 in guinea-pig isolated perfused lung.

The effects of infusions of bradykinin (0.2 microM), calcium ionophore A23187 (0.5 microM) and arachidonic acid (13 microM) on the release of eicosanoids from the guinea-pig isolated perfused lung were investigated using radioimmunoassay for thromboxane B2 (TXB2), 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha), PGE2, leukotriene B4 (LTB4) and LTC4 and bioassay using the superfusion cascade. Bradykinin released more 6-oxo-PGF1 alpha than TXB2, whereas arachidonic acid and ionophore released more TXB2 than 6-oxo-PGF1 alpha. The time course of eicosanoid release varied with the stimulus: bradykinin and arachidonic acid produced an immediate release, whereas the ionophore showed a slower onset of release. Although the amounts of LTB4 and LTC4 released by the ionophore were very low according to radioimmunoassays, there was evidence from the bioassay of release of a leukotriene-like substance, thought to be LTD4. The leukotriene antagonist FPL 55712 lacks specificity in the guinea-pig trachea; at the concentration used (2 microM) it antagonized contractions of the tracheal strip to PGE2 as well as to LTC4. Our results show that in the guinea-pig perfused lung the metabolism of exogenous arachidonic acid is both qualitatively and quantitatively different from the metabolism of endogenous arachidonic acid; furthermore, the profile of eicosanoid production is stimulus-dependent.