The contractile activities of lipoxin A₄ and lipoxin B₄ for guinea‐pig airway tissues

The isometric contractile activities of lipoxin A₄ (LxA₄) and lipoxin B₄ (LxB₄) were evaluated on guinea‐pig lung tissue over the concentration range, 10⁻⁸ to 10⁻⁵ m. LxA₄ contracted guinea‐pig lung parenchymal strips; the concentration eliciting 50% maximum histamine response was 3 × 10⁻⁶ m. LxA₄ did not contract tracheal spirals. The LxA₄ dose‐response curve was parallel to that of leukotriene D₄ (LTD₄) with LxA₄ being approximately 10,000 fold less potent than LTD₄. The time course of the contraction elicited by LxA₄ was similar to that of LTD₄ and it was slow in onset and did not plateau for 20 min. Pre‐incubation of parenchymal strips with leukotriene receptor antagonists at a concentration of 1 × 10⁻⁶ m to 3 × 10⁻⁵ m FPL 55712 or 3 × 10⁻⁵ m L 649923 inhibited LxA₄ activity. Pre‐incubation of tissues with 1 × 10⁻⁵ m L 651392, a 5‐lipoxygenase inhibitor, or 1 × 10⁻⁵ m indomethacin, a cyclo‐oxygenase inhibitor, did not affect the contractile activity of LxA₄. LxB₄ did not constrict parenchymal strips or tracheal spirals. 1988 British Pharmacological Society