Effect of inhibition of arachidonic acid metabolism on anaphylaxis of guinea pig lung strips

Abstract

The effect of inhibitors of the cyclooxygenase and/or lipoxygenase pathways of arachidonic acid metabolism on the anaphylactic contraction of lung parenchymal strips from ovalbumin sensitized guinea pigs was studied. Indomethacin, a selective cyclooxygenase inhibitor, significantly enhanced the anaphylactic contraction at 10⁻⁶ M with no effect at 10⁻⁵ or 10⁻⁴ M. By contrast, nordihydroguaiaretic acid (NDGA, 10⁻⁵ and 10⁻⁴ M), a lipoxygenase inhibitor, and 1-phenyl-3-pyrazolidinone (phenidone, 10⁻⁴ M), an inhibitor of both the cyclooxygenase and lipoxygenase markedly inhibited the anaphylactic contractile response. The pattern of inhibition was similar to that produced by FPL 55712, an antagonist of slow reacting substance of anaphylaxis (SRS-A), and was characterized by a decrease in the maximum tension and in the duration of the contraction. The results suggest that inhibition of the lipoxygenase pathway reduced anaphylactic contraction of guinea pig lung strips possibly by inhibiting the synthesis and release of SRS-A.