The effect of indomethacin on the contractile response of the guinea‐pig lung parenchymal strip to leukotrienes B4, C4, D4 and E4

Abstract

1 Indomethacin (1 μg ml⁻¹) almost totally inhibited the dose-dependent contractile response of isolated lung parenchymal strips of the guinea-pig (GPLS) to leukotriene B₄ (LTB₄) over the concentration range 0.18–18 nM. 2 LTC₄ (0.63 pM-63 nM)-induced contractions of GPLS were not significantly inhibited by indomethacin (1.0 and 10.0 μg ml⁻¹) except when the highest LTC₄ concentration (63 nM) was tested in the presence of indomethacin (10 μg ml⁻¹). 3 LTD₄ (1.3 fM-13 nM)-induced contractions of GPLS were not significantly inhibited by indomethacin (0.1–10 μg ml⁻¹) except for contractions induced by concentrations of LTD₄ greater than 0.13 nM and 13 nM. Indomethacin 1 μg ml⁻¹ and 10 μg ml⁻¹ inhibited the contractile response to 13 nM LTD₄ by 37 and 16% respectively. 4 LTE₄ (2.3 fM-23 nM)-induced contractions of GPLS were not significantly inhibited by indomethacin (0.1–10 μg ml⁻¹). Contraction due to LTE₄ 23 pM was significantly potentiated by indomethacin (1 μg ml⁻¹). 5 Clotrimazole (10 μM) significantly inhibited LTD₄-induced contractions of GPLS at concentrations greater than 13 pM but had no significant effect on LTC₄-induced contractions. 6 Cyclo-oxygenase products, probably principally thromboxane A₂, are important secondary mediators of LTB₄-induced contractions of GPLS but make little or no contribution to contractions of GPLS induced by LTC₄, LTD₄, and LTE₄, except at higher concentrations of LTD₄ and possibly LTC₄. Certain concentrations of LTE₄ may generate bronchodilator PGE₂ in GPLS.