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Comparison of the effects of indomethacin, RHC80267 and R59022 on superoxide production by 1,oleoyl‐2,acetyl glycerol and A23187 in human neutrophils
Author(s) -
Dale M. Maureen,
Penfield Adrienne
Publication year - 1987
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1987.tb11296.x
Subject(s) - diacylglycerol kinase , superoxide , chemistry , diacylglycerol lipase , protein kinase c , pharmacology , endocrinology , lipase , biochemistry , medicine , enzyme , biology
1 Indomethacin (10 −4 m ) causes marked augmentation of O − 2 release 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 O 2 ‐ 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.