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

Indomethacin (1 microgram 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. LTC4 (0.63 pM-63 nM)-induced contractions of GPLS were not significantly inhibited by indomethacin (1.0 and 10.0 micrograms ml-1) except when the highest LTC4 concentration (63 nM) was tested in the presence of indomethacin (10 micrograms ml-1). LTD4 (1.3 fM-13 nM)-induced contractions of GPLS were not significantly inhibited by indomethacin (0.1-10 micrograms ml-1) except for contractions induced by concentrations of LTD4 greater than 0.13 nM and 13 nM. Indomethacin 1 microgram ml-1 and 10 micrograms ml-1 inhibited the contractile response to 13 nM LTD4 by 37 and 16% respectively. LTE4 (2.3 fM-23 nM)-induced contractions of GPLS were not significantly inhibited by indomethacin (0.1-10 micrograms ml-1). Contraction due to LTE4 23 pM was significantly potentiated by indomethacin (1 microgram ml-1). Clotrimazole (10 microM) significantly inhibited LTD4-induced contractions of GPLS at concentrations greater than 13 pM but had no significant effect on LTC4-induced contractions. 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.