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

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Abstract
1 The effects of infusions of bradykinin (0.2 .mu.M), calcium ionophore A23187 (0.5 .mu.M) and arachidonic acid (13 .mu.M) 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. 2 Bradykinin released more 6-oxo-PGF1.alpha. than TXB2, whereas arachidonic acid and ionophore released more TXB2 than 6-oxo-PGF1.alpha.. 3 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. 4 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. 5 The leukotriene antagonist FPL 55712 lacks specificity in the guinea-pig trachea; at the concentration used (2 .mu.M) it antagonized contractions of the tracheal strip to PGE2 as well as to LTC4. 6 Our results showed 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.