Comparison of the effects of indomethacin, RHC80267 and R59022 on superoxide production by 1,oleoyl-2,acetyl glycerol and A23187 in human neutrophils

Abstract

1 Indomethacin (10⁻⁴ m) causes marked augmentation of O⁻₂release from human neutrophils when these are stimulated by either 1,oleoyl-2,acetylglycerol or the divalent cation ionophore, A23187, the concentration-response curve for each agent being shifted to the left and the maximum response to each increased. 2 The diacylglycerol kinase inhibitor, R59022 (10⁻⁵ m) has effects very similar to those of indomethacin on both the 1,oleoyl-2,acetylglycerol-induced and the A23187-induced concentration-response curves for O₂- generation. 3 The diacylglycerol lipase inhibitor, RHC80267 (10⁻⁵ m) on the other hand, has a similar effect to indomethacin on 1,oleoyl-2,acetylglycerol-induced O⁻₂ generation but, unlike indomethacin, has no effect on A23187-induced O⁻₂ generation. 4 Comparison of the effects of these three agents provides a clue to the locus of the action of indomethacin in increasing superoxide release, suggesting that it may act as a diacylglycerol kinase inhibitor. A component of diacylglycerol lipase inhibition may also be present. It is suggested that these results could have relevance for the use of indomethacin as an anti-inflammatory agent in chronic rheumatoid diseases.